bims-bac4me 2024-05-19 papers

bims-bac4me

Biomed News

on Microbiome and trained immunity

Issue of 2024‒05‒19
27 papers selected by
Chun-Chi Chang, University Hospital Zurich

Roles of airway and intestinal epithelia in responding to pathogens and maintaining tissue homeostasis.
Lipase-mediated detoxification of host-derived antimicrobial fatty acids by Staphylococcus aureus.
Editorial: Myeloid cell reprogramming: molecular pathways involved in disease development.
Endotoxin tolerance and trained immunity: breaking down immunological memory barriers.
Staphylococcus aureus-specific skin resident memory T cells protect against bacteria colonization but exacerbate atopic dermatitis-like flares in mice.
Interferon signaling in the nasal epithelium distinguishes among lethal and common cold coronaviruses and mediates viral clearance.
Structure-Function Relationships Of Mucociliary Clearance In Human Airways.
Opposing roles of resident and infiltrating immune cells in the defence against Legionella longbeachae via IL-18R/IFN-γ/ROS axis in mice.
Neutrophil-macrophage communication via extracellular vesicle transfer promotes itaconate accumulation and ameliorates cytokine storm syndrome.
Factors Affecting Neutrophil Functions During Sepsis: Human Microbiome and Epigenetics.
Mast cell-derived interleukin-4 mediates activation of dendritic cell during toll-like receptor 2-mediated inflammation.
Culturing Immortalized Human Airway Epithelial Cells at an Air-Liquid Interface for Measles Virus Infection.
Targeting respiratory microbiomes in COPD and bronchiectasis.
Cutaneous inflammasome driving ASC / gasdermin-D activation and IL-1β-secreting macrophages in severe atopic dermatitis.
CEBPA restricts alveolar type 2 cell plasticity during development and injury-repair.
Metabolism-inflammasome crosstalk shapes innate and adaptive immunity.
The Role of Prebiotics in Modulating Gut Microbiota: Implications for Human Health.
Classical monocyte ontogeny dictates their functions and fates as tissue macrophages.
Deletion of codY impairs Staphylococcus epidermidis biofilm formation, generation of viable but non-culturable cells and stimulates cytokine production in human macrophages.
The oxidant-antioxidant imbalance was involved in the pathogenesis of chronic rhinosinusitis with nasal polyps.
Macrophages in CRSwNP: Do they deserve more attention?
Pattern-recognition receptors and immunometabolic reprogramming: what we know and what to explore.
Green tea extract suppresses airway inflammation via oxidative stress-driven MAPKs/MMP-9 signaling in asthmatic mice and human airway epithelial cells.
Mechanical stretch preconditioned adipose-derived stem cells elicit polarization of anti-inflammatory M2-like macrophages and improve chronic wound healing.
Red Blood Cell DNA Capture and Delivery Drives Host Responses During Polymicrobial Sepsis.
Deciphering epigenetic regulations in the inflammatory pathways of atopic dermatitis.
Central carbon metabolism exhibits unique characteristics during the handling of fungal patterns by monocyte-derived dendritic cells.

Front Cell Infect Microbiol. 2024 ;14 1346087

Roles of airway and intestinal epithelia in responding to pathogens and maintaining tissue homeostasis.

Marcela Ambrogi, Chad M Vezina.

  Epithelial cells form a resilient barrier and orchestrate defensive and reparative mechanisms to maintain tissue stability. This review focuses on gut and airway epithelia, which are positioned where the body interfaces with the outside world. We review the many signaling pathways and mechanisms by which epithelial cells at the interface respond to invading pathogens to mount an innate immune response and initiate adaptive immunity and communicate with other cells, including resident microbiota, to heal damaged tissue and maintain homeostasis. We compare and contrast how airway and gut epithelial cells detect pathogens, release antimicrobial effectors, collaborate with macrophages, Tregs and epithelial stem cells to mount an immune response and orchestrate tissue repair. We also describe advanced research models for studying epithelial communication and behaviors during inflammation, tissue injury and disease.

Keywords:  barrier integrity; epithelial homeostasis; immune signaling; pathogen detection; tissue repair

DOI:  https://doi.org/10.3389/fcimb.2024.1346087
Commun Biol. 2024 May 15. 7(1): 572

Lipase-mediated detoxification of host-derived antimicrobial fatty acids by Staphylococcus aureus.

Arnaud Kengmo Tchoupa, Ahmed M A Elsherbini, Justine Camus, Xiaoqing Fu, Xuanheng Hu, Oumayma Ghaneme, Lea Seibert, Marco Lebtig, Marieke A Böcker, Anima Horlbeck, Stilianos P Lambidis, Birgit Schittek, Dorothee Kretschmer, Michael Lämmerhofer, Andreas Peschel.

Long-chain fatty acids with antimicrobial properties are abundant on the skin and mucosal surfaces, where they are essential to restrict the proliferation of opportunistic pathogens such as Staphylococcus aureus. These antimicrobial fatty acids (AFAs) elicit bacterial adaptation strategies, which have yet to be fully elucidated. Characterizing the pervasive mechanisms used by S. aureus to resist AFAs could open new avenues to prevent pathogen colonization. Here, we identify the S. aureus lipase Lip2 as a novel resistance factor against AFAs. Lip2 detoxifies AFAs via esterification with cholesterol. This is reminiscent of the activity of the fatty acid-modifying enzyme (FAME), whose identity has remained elusive for over three decades. In vitro, Lip2-dependent AFA-detoxification was apparent during planktonic growth and biofilm formation. Our genomic analysis revealed that prophage-mediated inactivation of Lip2 was rare in blood, nose, and skin strains, suggesting a particularly important role of Lip2 for host - microbe interactions. In a mouse model of S. aureus skin colonization, bacteria were protected from sapienic acid (a human-specific AFA) in a cholesterol- and lipase-dependent manner. These results suggest Lip2 is the long-sought FAME that exquisitely manipulates environmental lipids to promote bacterial growth in otherwise inhospitable niches.

DOI: https://doi.org/10.1038/s42003-024-06278-3
Front Immunol. 2024 ;15 1414482

Editorial: Myeloid cell reprogramming: molecular pathways involved in disease development.

Denise Risnik, Ana Colado, Enrique Podaza.



Keywords:  MDSC (myeloid-derived suppressor cell); macrophages; myeloid cell reprogramming; myeloid cells; trained immunity

DOI:  https://doi.org/10.3389/fimmu.2024.1414482
Front Immunol. 2024 ;15 1393283

Endotoxin tolerance and trained immunity: breaking down immunological memory barriers.

Eduardo López-Collazo, Carlos Del Fresno.

  For decades, innate immune cells were considered unsophisticated first responders, lacking the adaptive memory of their T and B cell counterparts. However, mounting evidence demonstrates the surprising complexity of innate immunity. Beyond quickly deploying specialized cells and initiating inflammation, two fascinating phenomena - endotoxin tolerance (ET) and trained immunity (TI) - have emerged. ET, characterized by reduced inflammatory response upon repeated exposure, protects against excessive inflammation. Conversely, TI leads to an enhanced response after initial priming, allowing the innate system to mount stronger defences against subsequent challenges. Although seemingly distinct, these phenomena may share underlying mechanisms and functional implications, blurring the lines between them. This review will delve into ET and TI, dissecting their similarities, differences, and the remaining questions that warrant further investigation.

Keywords:  endotoxin tolerance; innate immune memory; macrophage; monocyte; trained immunity

DOI:  https://doi.org/10.3389/fimmu.2024.1393283
J Allergy Clin Immunol. 2024 May 09. pii: S0091-6749(24)00460-3. [Epub ahead of print]

Staphylococcus aureus-specific skin resident memory T cells protect against bacteria colonization but exacerbate atopic dermatitis-like flares in mice.

Camille Braun, Cédric Badiou, Aurélie Guironnet-Paquet, Masashi Iwata, Vanina Lenief, Amandine Mosnier, Charlotte Beauclair, Emilie Renucci, Pauline Bouschon, Roxane Cuzin, Yoann Briend, Vijaykumar Patra, Sabine Patot, Tiffany C Scharschmidt, Willem van Wamel, Nicole Lemmens, Saeko Nakajima, François Vandenesh, Jean-François Nicolas, Gérard Lina, Audrey Nosbaum, Marc Vocanson.

  BACKGROUND: The contribution of Staphylococcus aureus (S. aureus) to the exacerbation of atopic dermatitis (AD) is widely documented, but its role as a primary trigger of AD skin symptoms remains poorly explored.OBJECTIVE: To reappraise the main bacterial factors and underlying immune mechanisms by which S. aureus triggers AD-like inflammation.
METHODS: We capitalized on a pre-clinical model, in which different clinical isolates were applied in the absence of any prior experimental skin injury.
RESULTS: We report that the development of S. aureus-induced dermatitis depended on the nature of the S. aureus strain, its viability, the concentration of the applied bacterial suspension, the production of secreted and non-secreted factors, as well as the activation of accessory gene regulatory quorum sensing system. In addition, the rising dermatitis, which exhibited the well-documented AD cytokine signature, was significantly inhibited in inflammasome adaptor protein ASC- and monocyte/macrophage-deficient animals, but not in T- and B-cell-deficient mice, suggesting a major role for the innate response in the induction of skin inflammation. However, bacterial exposure generated a robust adaptive immune response against S. aureus, and an accumulation of S. aureus-specific γδ and CD4+ tissue resident memory T (Trm) cells at the site of previous dermatitis. The latter both contributed to worsen the flares of AD-like dermatitis upon new bacteria exposures, but also, protected the mice from persistent bacterial colonization.
CONCLUSION: These data highlight the induction of unique AD-like inflammation, with the generation of pro-inflammatory but protective Trm cells in a context of natural exposure to pathogenic S. aureus strains.

Keywords:  Atopic dermatitis; Innate response; Natural exposure; Skin colonization; Staphylococcus aureus; T resident memory cells

DOI:  https://doi.org/10.1016/j.jaci.2024.03.032
Proc Natl Acad Sci U S A. 2024 May 21. 121(21): e2402540121

Interferon signaling in the nasal epithelium distinguishes among lethal and common cold coronaviruses and mediates viral clearance.

Clayton J Otter, David M Renner, Alejandra Fausto, Li Hui Tan, Noam A Cohen, Susan R Weiss.

  All respiratory viruses establish primary infections in the nasal epithelium, where efficient innate immune induction may prevent dissemination to the lower airway and thus minimize pathogenesis. Human coronaviruses (HCoVs) cause a range of pathologies, but the host and viral determinants of disease during common cold versus lethal HCoV infections are poorly understood. We model the initial site of infection using primary nasal epithelial cells cultured at an air-liquid interface (ALI). HCoV-229E, HCoV-NL63, and human rhinovirus-16 are common cold-associated viruses that exhibit unique features in this model: early induction of antiviral interferon (IFN) signaling, IFN-mediated viral clearance, and preferential replication at nasal airway temperature (33 °C) which confers muted host IFN responses. In contrast, lethal SARS-CoV-2 and MERS-CoV encode antagonist proteins that prevent IFN-mediated clearance in nasal cultures. Our study identifies features shared among common cold-associated viruses, highlighting nasal innate immune responses as predictive of infection outcomes and nasally directed IFNs as potential therapeutics.

Keywords:  common cold; coronavirus; interferon signaling; nasal epithelium; virus

DOI:  https://doi.org/10.1073/pnas.2402540121
Res Sq. 2024 Apr 25. pii: rs.3.rs-4164522. [Epub ahead of print]

Structure-Function Relationships Of Mucociliary Clearance In Human Airways.

Amy Ryan, Doris Roth, Ayse Tugce Sahin, Feng Ling, Christiana Senger, Erik Quiroz, Ben Calvert, Anne van der Does, Tankut Güney, Annemarie van Schadewijk, Laura von Schledorn, Ruth Olmer, Eva Kanso, Janna Nawroth, Niels Tepho, Sarah Glasl.

Our study focuses on the intricate connection between tissue-level organization and ciliated organ function in humans, particularly in understanding the morphological organization of airways and their role in mucociliary clearance. Mucociliary clearance is a key mechanical defense mechanism of human airways, and clearance failure is associated with many respiratory diseases, including chronic obstructive pulmonary disease (COPD) and asthma. While single-cell transcriptomics have unveiled the cellular complexity of the human airway epithelium, our understanding of the mechanics that link epithelial structure to clearance function mainly stem from animal models. This reliance on animal data limits crucial insights into human airway barrier function and hampers the human-relevant in vitro modeling of airway diseases. This study, for the first time, maps the distribution of ciliated and secretory cell types along the airway tree in both rats and humans, noting species-specific differences in ciliary function and elucidates structural parameters of airway epithelia that predict clearance function in both native and in vitro tissues alike. By uncovering how tissue organization influences ciliary function, we can better understand disruptions in mucociliary clearance, which could have implications for various ciliated organs beyond the airways.

DOI: https://doi.org/10.21203/rs.3.rs-4164522/v1
Mucosal Immunol. 2024 May 13. pii: S1933-0219(24)00042-4. [Epub ahead of print]

Opposing roles of resident and infiltrating immune cells in the defence against Legionella longbeachae via IL-18R/IFN-γ/ROS axis in mice.

Lara M Oberkircher, Victoria M Scheiding, H Linda Rafeld, Eric Hanssen, Jan N Hansen, Markus J Fleischmann, Nina Kessler, David Pitsch, Dagmar Wachten, Wolfgang Kastenmüller, Andrew S Brown, Elizabeth L Hartland, Ian R van Driel, Garrett Z Ng, Natalio Garbi.

  The immune response against Legionella longbeachae, a causative agent of the often-fatal Legionnaires' pneumonia, is poorly understood. Here we investigated the specific roles of tissue-resident alveolar macrophages (AM) and infiltrating phagocytes during infection with this pathogen. AM were the predominant cell type that internalized bacteria one day after infection. Three and five days after infection, AM numbers were greatly reduced while there was an influx of neutrophils and later monocyte-derived cells (MC) into lung tissue. AM carried greater numbers of viable L.longbeachae than neutrophils and MC, which correlated with a higher capacity of L.longbeachae to translocate bacterial effector proteins required for bacterial replication into the AM cytosol. Cell ablation experiments demonstrated that AM promoted infection whereas neutrophils and MC were required for efficient bacterial clearance. IL-18 was important for IFN-γ production by IL-18R+ NK cells and T cells which, in turn, stimulated ROS-mediated bactericidal activity in neutrophils resulting in restriction of L.longbeachae infection. Ciliated bronchiolar epithelial cells also expressed IL-18R but did not play a role in IL-18-mediated L.longbeachae clearance. Our results have identified opposing innate functions of tissue-resident and infiltrating immune cells during L.longbeachae infection that may be manipulated to improve protective responses.

Keywords:  IFN-γ; Interleukin 18; Legionella; ROS; monocyte-derived macrophages; monocytes; neutrophils; tissue-resident macrophages

DOI:  https://doi.org/10.1016/j.mucimm.2024.05.001
Cell Mol Immunol. 2024 May 14.

Neutrophil-macrophage communication via extracellular vesicle transfer promotes itaconate accumulation and ameliorates cytokine storm syndrome.

Haixia Kang, Ting Liu, Yuanyuan Wang, Wenjuan Bai, Yan Luo, Jing Wang.

  Cytokine storm syndrome (CSS) is a life-threatening systemic inflammatory syndrome involving innate immune hyperactivity triggered by various therapies, infections, and autoimmune conditions. However, the potential interplay between innate immune cells is not fully understood. Here, using poly I:C and lipopolysaccharide (LPS)-induced cytokine storm models, a protective role of neutrophils through the modulation of macrophage activation was identified in a CSS model. Intravital imaging revealed neutrophil-derived extracellular vesicles (NDEVs) in the liver and spleen, which were captured by macrophages. NDEVs suppressed proinflammatory cytokine production by macrophages when cocultured in vitro or infused into CSS models. Metabolic profiling of macrophages treated with NDEV revealed elevated levels of the anti-inflammatory metabolite, itaconate, which is produced from cis-aconitate in the Krebs cycle by cis-aconitate decarboxylase (Acod1, encoded by Irg1). Irg1 in macrophages, but not in neutrophils, was critical for the NDEV-mediated anti-inflammatory effects. Mechanistically, NDEVs delivered miR-27a-3p, which suppressed the expression of Suclg1, the gene encoding the enzyme that metabolizes itaconate, thereby resulting in the accumulation of itaconate in macrophages. These findings demonstrated that neutrophil-to-macrophage communication mediated by extracellular vesicles is critical for promoting the anti-inflammatory reprogramming of macrophages in CSS and may have potential implications for the treatment of this fatal condition.

Keywords:  Cytokine storm syndrome; Extracellular vesicle; Itaconate; Macrophage; Neutrophil

DOI:  https://doi.org/10.1038/s41423-024-01174-6
J Leukoc Biol. 2024 May 12. pii: qiae107. [Epub ahead of print]

Factors Affecting Neutrophil Functions During Sepsis: Human Microbiome and Epigenetics.

Yina Ma, Yu Zhao, Xin Zhang.

  Sepsis is a severe disease that occurs when the body's immune system reacts excessively to infection. The body's response, which includes an intense anti-bacterial reaction, can damage its tissues and organs. Neutrophils are the major components of white blood cells in circulation and play a vital role in innate immunity while fighting against infections, and are considered a feature determining sepsis classification. There's a plethora of basic research detailing neutrophil functioning, among which, the study of neutrophil extracellular traps (NETs) is providing novel insights into mechanisms and treatments of sepsis. This review explores their functions, dysfunctions, and influences in the context of sepsis. The interplay between neutrophils and the human microbiome and the impact of DNA methylation on neutrophil function in sepsis are crucial areas of study. The interaction between neutrophils and the human microbiome is complex, particularly in the context of sepsis where dysbiosis may occur. We highlight the importance of deciphering neutrophil's functional alterations and their epigenetic features in sepsis because it is critical for defining sepsis endotypes and opening up the possibility for novel diagnostic methods and therapy. Specifically, epigenetic signatures are pivotal since they will provide a novel implication for sepsis diagnostic method when used in combination with the cell-free DNA (cfDNA). Research is exploring how specific patterns of DNA methylation in neutrophils, detectable in cfDNA, could serve as biomarkers for the early detection of sepsis.

Keywords:  cfDNA; epigenetics; gut microbiome; neutrophil; trained immunity

DOI:  https://doi.org/10.1093/jleuko/qiae107
Front Immunol. 2024 ;15 1353922

Mast cell-derived interleukin-4 mediates activation of dendritic cell during toll-like receptor 2-mediated inflammation.

Joschua Friedel, Sandra Pierre, Anja Kolbinger, Tim J Schäufele, Blerina Aliraj, Andreas Weigert, Klaus Scholich.

  Introduction: During an innate inflammation, immune cells form distinct pro- and anti-inflammatory regions around pathogen-containing core-regions. Mast cells are localized in an anti-inflammatory microenvironment during the resolution of an innate inflammation, suggesting antiinflammatory roles of these cells.Methods: High-content imaging was used to investigated mast cell-dependent changes in the regional distribution of immune cells during an inflammation, induced by the toll-like receptor (TLR)-2 agonist zymosan.
Results: The distance between the zymosan-containing core-region and the anti-inflammatory region, described by M2-like macrophages, increased in mast cell-deficient mice. Absence of mast cells abolished dendritic cell (DC) activation, as determined by CD86-expression and localized the DCs in greater distance to zymosan particles. The CD86- DCs had a higher expression of the pro-inflammatory interleukins (IL)-1β and IL-12/23p40 as compared to activated CD86+ DCs. IL-4 administration restored CD86 expression, cytokine expression profile and localization of the DCs in mast cell-deficient mice. The IL-4 effects were mast cell-specific, since IL-4 reduction by eosinophil depletion did not affect activation of DCs.
Discussion: We found that mast cells induce DC activation selectively at the site of inflammation and thereby determine their localization within the inflammation. Overall, mast cells have antiinflammatory functions in this inflammation model and limit the size of the pro-inflammatory region surrounding the zymosan-containing core region.

Keywords:  dendritic cells; high-content immunohistochemistry; inflammatory structure; mast cells; toll-like receptor 2

DOI:  https://doi.org/10.3389/fimmu.2024.1353922
Methods Mol Biol. 2024 ;2808 141-152

Culturing Immortalized Human Airway Epithelial Cells at an Air-Liquid Interface for Measles Virus Infection.

Justin W Kaufman, Brajesh K Singh, Ni Li, Patrick L Sinn.

  Measles virus (MeV) infection of airway surface epithelial cells provides a site for final amplification before being released back into the environment via coughing and sneezing. Multiple cell lines have served as models of polarized epithelia for MeV infection, such as Caco2 cells (intestinal derived human epithelia) or MDCK cells (kidney derived canine epithelia). In this chapter, we describe the materials and air-liquid interface (ALI) culture conditions for maintaining four different cell lines derived from human airway epithelial cells: 16HBE14o-, Calu-3, H358, and NuLi-1. We provide methods for confirming transepithelial electrical resistance (TER) and preparing samples for microscopy as well as expected results from apical or basolateral MeV delivery. Polarized human airway derived cells serve as tissue culture models for investigating targeted questions about how MeV exits a human host. In addition, these methods are generalizable to studies of other respiratory viruses or the biology of ALI airway epithelial cells.

Keywords:  Differentiate; Lung; Paramyxovirus; Polarize; Respiratory cells; Respiratory virus

DOI:  https://doi.org/10.1007/978-1-0716-3870-5_11
Expert Rev Respir Med. 2024 May 14.

Targeting respiratory microbiomes in COPD and bronchiectasis.

Sanjay H Chotirmall, Micheál Mac Aogáin, Pei Yee Tiew, Tavleen Kaur Jaggi, Jayanth Kumar Narayana, Shivani Singh, Philip M Hansbro, Leopoldo N Segal.

  INTRODUCTION: This review summarizes our current understanding of the respiratory microbiome in COPD and Bronchiectasis. We explore the interplay between microbial communities, host immune responses, disease pathology and treatment outcomes.AREAS COVERED: We detail the dynamics of the airway microbiome, its influence in chronic respiratory diseases, and analytical challenges. Relevant articles from PubMed and Medline searches between Jan 2010 and March 2024 were retrieved and summarized. The review examines clinical correlations of the microbiome in COPD and bronchiectasis, assessing how current therapies impact upon it. The potential of emerging immunotherapies, anti-inflammatories and antimicrobial strategies are discussed, with focus on the pivotal role of commensal taxa in maintaining respiratory health and the promising avenue of microbiome remodeling for disease management.
EXPERT OPINION: Given the heterogeneity in microbiome composition and its pivotal role in disease development and progression, a shift toward microbiome-directed therapeutics is appealing. This transition, from traditional 'pathogen-centric' diagnostic and treatment modalities to those acknowledging the microbiome, can be enabled by evolving cross-disciplinary platforms which have the potential to accelerate microbiome-based interventions into routine clinical practice. Bridging the gap between comprehensive microbiome analysis and clinical application, however, remains challenging, necessitating continued innovation in research, diagnostics, trials and therapeutic development pipelines.

Keywords:  Bronchiectasis; COPD; Immunopathology; Metagenomics; Microbiome

DOI:  https://doi.org/10.1080/17476348.2024.2355155
Arch Dermatol Res. 2024 May 11. 316(5): 156

Cutaneous inflammasome driving ASC / gasdermin-D activation and IL-1β-secreting macrophages in severe atopic dermatitis.

Yasmim Álefe Leuzzi Ramos, Naiura Vieira Pereira, Valeria Aoki, Mírian Nacagami Sotto, Joyce Tiyeko Kawakami, Luiz Fernando Ferraz da Silva, Maria Notomi Sato, Raquel Leão Orfali.

  Atopic dermatitis (AD) is an inflammatory skin disease with intense pruritus, and chronic skin colonization by Staphylococcus aureus. To understand the inflammatory status in AD, we investigated the inflammasome complex, that activates ASC (Apoptosis-associated speck-like protein containing a CARD), caspase-1 and GSDMD (gasdermin-D), and production of IL-1β and IL-18. We aimed to evaluate the expression of the inflammasome pathway in the skin of adults with AD. Thirty patients with moderate to severe AD and 20 healthy controls were enrolled in the study. We performed the analysis of the inflammasome components NLRP1, NLRP3, AIM-2, IL-1β, IL-18, Caspase-1, ASC, GSDMD, and CD68 expression (macrophage marker) by immunohistochemistry and immunofluorescence. The main findings included increased expression of NLRP3, NLRP1 and AIM-2 at dermal level of severe AD; augmented IL-18 and IL-1β expression at epidermis of moderate and severe patients, and in the dermis of severe AD; augmented expression of ASC, caspase-1 and GSDMD in both epidermis and dermis of moderate and severe AD. We detected positive correlation between caspase-1, GSDMD and IL-1β (epidermis) and caspase-1 (dermis) and AD severity; NLRP3, AIM-2 and IL-1β, and NLRP3 with IL-18 in the epidermis; ASC, GSDMD and IL-1β, and NLRP3, AIM-2, caspase-1, and IL-18 in the dermis. We also evidenced the presence of CD68+ macrophages secreting GSDMD, ASC and IL-1β in moderate and severe AD. Cutaneous macrophages, early detected in moderate AD, have its role in the disease inflammatory mechanisms. Our study indicates a canonical activation pathway of inflammasomes, reinforced by the chronic status of inflammation in AD. The analysis of the inflammasome complex evidenced an imbalance in its regulation, with increased expression of the evaluated components, which is remarkably in severe AD, emphasizing its relevance as potential disease biomarkers and targets for immunomodulatory interventions.

Keywords:  Atopic dermatitis; IL-1β; Inflammasome; Keratinocytes; Macrophage; gasdermin-D

DOI:  https://doi.org/10.1007/s00403-024-02899-0
Nat Commun. 2024 May 16. 15(1): 4148

CEBPA restricts alveolar type 2 cell plasticity during development and injury-repair.

Dalia Hassan, Jichao Chen.

Cell plasticity theoretically extends to all possible cell types, but naturally decreases as cells differentiate, whereas injury-repair re-engages the developmental plasticity. Here we show that the lung alveolar type 2 (AT2)-specific transcription factor (TF), CEBPA, restricts AT2 cell plasticity in the mouse lung. AT2 cells undergo transcriptional and epigenetic maturation postnatally. Without CEBPA, both neonatal and mature AT2 cells reduce the AT2 program, but only the former reactivate the SOX9 progenitor program. Sendai virus infection bestows mature AT2 cells with neonatal plasticity where Cebpa mutant, but not wild type, AT2 cells express SOX9, as well as more readily proliferate and form KRT8/CLDN4+ transitional cells. CEBPA promotes the AT2 program by recruiting the lung lineage TF NKX2-1. The temporal change in CEBPA-dependent plasticity reflects AT2 cell developmental history. The ontogeny of AT2 cell plasticity and its transcriptional and epigenetic mechanisms have implications in lung regeneration and cancer.

DOI: https://doi.org/10.1038/s41467-024-48632-3
Cell Chem Biol. 2024 May 16. pii: S2451-9456(24)00168-5. [Epub ahead of print]31(5): 884-903

Metabolism-inflammasome crosstalk shapes innate and adaptive immunity.

Jun Wu, Xuan Sun, Peng Jiang.

Inflammasomes are a central component of innate immunity and play a vital role in regulating innate immune response. Activation of inflammasomes is also indispensable for adaptive immunity, modulating the development and response of adaptive immunity. Recently, increasing studies have shown that metabolic alterations and adaptations strongly influence and regulate the differentiation and function of the immune system. In this review, we will take a holistic view of how inflammasomes bridge innate and adaptive (especially T cell) immunity and how inflammasomes crosstalk with metabolic signals during the immune responses. And, special attention will be paid to the metabolic control of inflammasome-mediated interactions between innate and adaptive immunity in disease. Understanding the metabolic regulatory functions of inflammasomes would provide new insights into future research directions in this area and may help to identify potential targets for inflammasome-associated diseases and broaden therapeutic avenues.

DOI: https://doi.org/10.1016/j.chembiol.2024.04.006
Int J Mol Sci. 2024 Apr 29. pii: 4834. [Epub ahead of print]25(9):

The Role of Prebiotics in Modulating Gut Microbiota: Implications for Human Health.

Suyeon Yoo, Suk-Chae Jung, Kihyuck Kwak, Jun-Seob Kim.

  The human gut microbiota, an intricate ecosystem within the gastrointestinal tract, plays a pivotal role in health and disease. Prebiotics, non-digestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of beneficial microorganisms, have emerged as a key modulator of this complex microbial community. This review article explores the evolution of the prebiotic concept, delineates various types of prebiotics, including fructans, galactooligosaccharides, xylooligosaccharides, chitooligosaccharides, lactulose, resistant starch, and polyphenols, and elucidates their impact on the gut microbiota composition. We delve into the mechanisms through which prebiotics exert their effects, particularly focusing on producing short-chain fatty acids and modulating the gut microbiota towards a health-promoting composition. The implications of prebiotics on human health are extensively reviewed, focusing on conditions such as obesity, inflammatory bowel disease, immune function, and mental health. The review further discusses the emerging concept of synbiotics-combinations of prebiotics and probiotics that synergistically enhance gut health-and highlights the market potential of prebiotics in response to a growing demand for functional foods. By consolidating current knowledge and identifying areas for future research, this review aims to enhance understanding of prebiotics' role in health and disease, underscoring their importance in maintaining a healthy gut microbiome and overall well-being.

Keywords:  human health; intestinal microbiota; microbiota; prebiotics

DOI:  https://doi.org/10.3390/ijms25094834
Immunity. 2024 May 10. pii: S1074-7613(24)00224-3. [Epub ahead of print]

Classical monocyte ontogeny dictates their functions and fates as tissue macrophages.

Sébastien Trzebanski, Jung-Seok Kim, Niss Larossi, Ayala Raanan, Daliya Kancheva, Jonathan Bastos, Montaser Haddad, Aryeh Solomon, Ehud Sivan, Dan Aizik, Jarmila Sekeresova Kralova, Mor Gross-Vered, Sigalit Boura-Halfon, Tsvee Lapidot, Ronen Alon, Kiavash Movahedi, Steffen Jung.

  Classical monocytes (CMs) are ephemeral myeloid immune cells that circulate in the blood. Emerging evidence suggests that CMs can have distinct ontogeny and originate from either granulocyte-monocyte- or monocyte-dendritic-cell progenitors (GMPs or MDPs). Here, we report surface markers that allowed segregation of murine GMP- and MDP-derived CMs, i.e., GMP-Mo and MDP-Mo, as well as their functional characterization, including fate definition following adoptive cell transfer. GMP-Mo and MDP-Mo yielded an equal increase in homeostatic CM progeny, such as blood-resident non-classical monocytes and gut macrophages; however, these cells differentially seeded various other selected tissues, including the dura mater and lung. Specifically, GMP-Mo and MDP-Mo differentiated into distinct interstitial lung macrophages, linking CM dichotomy to previously reported pulmonary macrophage heterogeneity. Collectively, we provide evidence for the existence of two functionally distinct CM subsets in the mouse that differentially contribute to peripheral tissue macrophage populations in homeostasis and following challenge.

Keywords:  CM; GMP-Mo; MDP-Mo; dura mater; influenza; lung; macrophages; monocytes; monopoiesis

DOI:  https://doi.org/10.1016/j.immuni.2024.04.019
J Med Microbiol. 2024 May;73(5):

Deletion of codY impairs Staphylococcus epidermidis biofilm formation, generation of viable but non-culturable cells and stimulates cytokine production in human macrophages.

Nathalie Lopes, Renato B Pereira, Alexandra Correia, Manuel Vilanova, Nuno Cerca, Angela França.

  Introduction.Staphylococcus epidermidis biofilms are one of the major causes of bloodstream infections related to the use of medical devices. The diagnosis of these infections is challenging, delaying their treatment and resulting in increased morbidity and mortality rates. As such, it is urgent to characterize the mechanisms employed by this bacterium to endure antibiotic treatments and the response of the host immune system, to develop more effective therapeutic strategies. In several bacterial species, the gene codY was shown to encode a protein that regulates the expression of genes involved in biofilm formation and immune evasion. Additionally, in a previous study, our group generated evidence indicating that codY is involved in the emergence of viable but non-culturable (VBNC) cells in S. epidermidis.Gap statement/Hypothesis. As such, we hypothesized that the gene codY has have an important role in this bacterium virulence.Aim. This study aimed to assess, for the first time, the impact of the deletion of the gene codY in S. epidermidis virulence, namely, in antibiotic susceptibility, biofilm formation, VBNC state emergence and in vitro host immune system response.Methodology. Using an allelic replacement strategy, we constructed and then characterized an S. epidermidis strain lacking codY, in regards to biofilm and VBNC cell formation, susceptibility to antibiotics as well as their role in the interaction with human blood and plasma. Additionally, we investigate whether the codY gene can impact the activation of innate immune cells by evaluating the production of both pro- and anti-inflammatory cytokines by THP-1 macrophages.Results. We demonstrated that the deletion of the gene codY resulted in biofilms with less c.f.u. counts and fewer VBNC cells. Furthermore, we show that although WT and mutant cells were similarly internalized in vitro by human macrophages, a stronger cytokine response was elicited by the mutant in a toll-like receptor 4-dependent manner.Conclusion. Our results indicate that codY contributes to S. epidermidis virulence, which in turn may have an impact on our ability to manage the biofilm-associated infections caused by this bacterium.

Keywords:  antibiotics; biofilms; cytokines; human blood; human macrophages; phagocytosis

DOI:  https://doi.org/10.1099/jmm.0.001837
Front Immunol. 2024 ;15 1380846

The oxidant-antioxidant imbalance was involved in the pathogenesis of chronic rhinosinusitis with nasal polyps.

Jing Zhou, Jiao Zhou, Ruowu Liu, Yafeng Liu, Juan Meng, Qiao Wen, Yirui Luo, Shixi Liu, Huabin Li, Luo Ba, Jintao Du.

  Background: Although oxidative stress is involved in the pathophysiological process of chronic rhinosinusitis with nasal polyps (CRSwNP), the specific underlying mechanism is still unclear. Whether antioxidant therapy can treat CRSwNP needs further investigation.Methods: Immunohistochemistry, immunofluorescence, western blotting and quantitative polymerase chain reaction (qPCR) analyses were performed to detect the distribution and expression of oxidants and antioxidants in nasal polyp tissues. qPCR revealed correlations between oxidase, antioxidant enzymes and inflammatory cytokine levels in CRSwNP patients. Human nasal epithelial cells (HNEpCs) and primary macrophages were cultured to track the cellular origin of oxidative stress in nasal polyps(NPs) and to determine whether crocin can reduce cellular inflammation by increasing the cellular antioxidant capacity.
Results: The expression of NOS2, NOX1, HO-1 and SOD2 was increased in nasal epithelial cells and macrophages derived from nasal polyp tissue. Oxidase levels were positively correlated with those of inflammatory cytokines (IL-5 and IL-6). Conversely, the levels of antioxidant enzymes were negatively correlated with those of IL-13 and IFN-γ. Crocin inhibited M1 and M2 macrophage polarization as well as the expression of NOS2 and NOX1 and improved the antioxidant capacity of M2 macrophages. Moreover, crocin enhanced the ability of antioxidants to reduce inflammation via the KEAP1/NRF2/HO-1 pathway in HNEpCs treated with SEB or LPS. Additionally, we observed the antioxidant and anti-inflammatory effects of crocin in nasal explants.
Conclusion: Oxidative stress plays an important role in the development of CRSwNP by promoting various types of inflammation. The oxidative stress of nasal polyps comes from epithelial cells and macrophages. Antioxidant therapy may be a promising strategy for treating CRSwNP.

Keywords:  CRSwNP; Nrf2; macrophages; nasal epithelial cells; oxidative stress

DOI:  https://doi.org/10.3389/fimmu.2024.1380846
Int Immunopharmacol. 2024 May 13. pii: S1567-5769(24)00755-0. [Epub ahead of print]134 112236

Macrophages in CRSwNP: Do they deserve more attention?

Hong-Li Fan, Zhou-Tong Han, Xin-Ru Gong, Yu-Qi Wu, Yi-Jie Fu, Tian-Min Zhu, Hui Li.

  Chronic rhinosinusitis (CRS) represents a heterogeneous disorder primarily characterized by the persistent inflammation of the nasal cavity and paranasal sinuses. The subtype known as chronic rhinosinusitis with nasal polyposis (CRSwNP) is distinguished by a significantly elevated recurrence rate and augmented challenges in the management of nasal polyps. The pathogenesis underlying this subtype remains incompletely understood. Macrophages play a crucial role in mediating the immune system's response to inflammatory stimuli. These cells exhibit remarkable plasticity and heterogeneity, differentiating into either the pro-inflammatory M1 phenotype or the anti-inflammatory and reparative M2 phenotype depending on the surrounding microenvironment. In CRSwNP, macrophages demonstrate reduced production of Interleukin 10 (IL-10), compromised phagocytic activity, and decreased autophagy. Dysregulation of pro-resolving mediators may occur during the inflammatory resolution process, which could potentially hinder the adequate functioning of anti-inflammatory macrophages in facilitating resolution. Collectively, these factors may contribute to the prolonged inflammation observed in CRSwNP. Additionally, macrophages may enhance fibrin cross-linking through the release of factor XIII-A (FAXIII), promoting fibrin deposition and plasma protein retention. Macrophages also modulate vascular permeability by releasing Vascular endothelial growth factor (VEGF). Moreover, they may disrupt the balance between Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of Metalloproteinases (TIMPs), which favors extracellular matrix (ECM) degradation, edema formation, and pseudocyst development. Accumulating evidence suggests a close association between macrophage infiltration and CRSwNP; however, the precise mechanisms underlying this relationship warrant further investigation. In different subtypes of CRSwNP, different macrophage phenotypic aggregations trigger different types of inflammatory features. Increasing evidence suggests that macrophage infiltration is closely associated with CRSwNP, but the mechanism and the relationship between macrophage typing and CRSwNP endophenotyping remain to be further explored. This review discusses the role of different types of macrophages in the pathogenesis of different types of CRSwNP and their contribution to polyp formation, in the hope that a better understanding of the role of macrophages in specific CRSwNP will contribute to a precise and individualized understanding of the disease.

Keywords:  Chronic rhinosinusitis; FXIII-A; IL-10; Macrophages; SPM

DOI:  https://doi.org/10.1016/j.intimp.2024.112236
J Innate Immun. 2024 May 13.

Pattern-recognition receptors and immunometabolic reprogramming: what we know and what to explore.

Vijay Kumar, John H Stewart Iv.

BACKGROUND: Evolutionarily, immune response is a complex mechanism that protects the host from internal and external threats. Pattern recognition receptors (PRRs) recognize MAMPs, PAMPs, and DAMPs to initiate a protective pro-inflammatory immune response. PRRs are expressed on the cell membranes by TLR1, 2, 4, and 6 and in the cytosolic organelles by TLR3, 7, 8, and 9, NLRs, ALRs, and cGLRs. We know their downstream signaling pathways controlling immunoregulatory and pro-inflammatory immune response. However, the impact of PRRs on metabolic control of immune cells to control their pro- and anti-inflammatory activity has not been discussed extensively.SUMMARY: Immune cell metabolism or immunometabolism critically determines immune cells' pro-inflammatory phenotype and function. The current article discusses immunometabolic reprogramming (IR) upon activation of different PRRs, such as TLRs, NLRs, cGLRs, and RLRs. The duration and type of PRR activated, species studied, and location of immune cells to specific organ are critical factors to determine the IR-induced immune response.
KEY MESSAGE: The work herein describes IR upon TLR, NLR, cGLR, and RLR activation. Understanding IR upon activating different PRRs is critical for designing better immune cell-specific immunotherapeutics and immunomodulators targeting inflammation and inflammatory diseases.

DOI: https://doi.org/10.1159/000539278
Front Immunol. 2024 ;15 1362404

Green tea extract suppresses airway inflammation via oxidative stress-driven MAPKs/MMP-9 signaling in asthmatic mice and human airway epithelial cells.

Jeong-Won Kim, Jin-Hwa Kim, Ji-Soo Jeong, Chang-Yeop Kim, Eun-Hye Chung, Sung-Hwan Kim, Eui-Ju Hong, Hyo-Jung Kwon, Je-Won Ko, Tae-Won Kim.

  Introduction: The anti-inflammatory effect of green tea extract (GTE) has been confirmed in asthmatic mice, however, the pharmacological mechanism is not fully elucidated.Methods: To investigate the therapeutic efficacy of GTE in asthma and identify specific pathways, murine model of allergic asthma was established by ovalbumin (OVA) sensitization and the challenge for 4 weeks, with oral treatment using GTE and dexamethasone (DEX). Inflammatory cell counts, cytokines, OVA-specific IgE, airway hyperreactivity, and antioxidant markers in the lung were evaluated. Also, pulmonary histopathological analysis and western blotting were performed. In vitro, we established the model by stimulating the human airway epithelial cell line NCI-H292 using lipopolysaccharide, and treating with GTE and mitogen-activated protein kinases (MAPKs) inhibitors.
Results: The GTE100 and GTE400 groups showed a decrease in airway hyperresponsiveness and the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) compared to the OVA group. GTE treatment also reduced interleukin (IL)-13, IL-5, and IL-4 levels in the BALF, and OVA-specific immunoglobulin E levels in the serum compared to those in the OVA group. GTE treatment decreased OVA-induced mucus secretion and airway inflammation. In addition, GTE suppressed the oxidative stress, and phosphorylation of MAPKs, which generally occurs after exposure to OVA. GTE administration also reduced matrix metalloproteinase-9 activity and protein levels.
Conclusion: GTE effectively inhibited asthmatic respiratory inflammation and mucus hyperproduction induced by OVA inhalation. These results suggest that GTE has the potential to be used for the treatment of asthma.

Keywords:  asthma; green tea extract; inflammation; matrix metalloproteinase-9; mitogen-activated protein kinase signaling; oxidative stress

DOI:  https://doi.org/10.3389/fimmu.2024.1362404
FASEB J. 2024 May 31. 38(10): e23626

Mechanical stretch preconditioned adipose-derived stem cells elicit polarization of anti-inflammatory M2-like macrophages and improve chronic wound healing.

Jiahao He, Shengzhou Shan, Taoran Jiang, Sizheng Zhou, Jiaqi Qin, Qingfeng Li, Zheyuan Yu, Dejun Cao, Bin Fang.

  Transplantation of adipose-derived stem cells (ASCs) is a promising option in the field of chronic wounds treatment. However, the effectiveness of ASCs therapies has been hampered by highly inflammatory environment in chronic wound areas. These problems could be partially circumvented using efficient approaches that boost the survival and anti-inflammatory capacity of transplanted ASCs. Here, by application of mechanical stretch (MS), we show that ASCs exhibits increased survival and immunoregulatory properties in vitro. MS triggers the secretion of macrophage colony stimulating factor (M-CSF) from ASCs, a chemokine that is linked to anti-inflammatory M2-like macrophages polarization. When the MS-ASCs were transplanted to chronic wounds, the wound area yields significantly faster closure rate and lower inflammatory mediators, largely due to macrophages polarization driven by transplanted MS-ASCs. Thus, our work shows that mechanical stretch can be harnessed to enhance ASCs transplantation efficiency in chronic wounds treatment.

Keywords:  adipose‐derived stem cells; anti‐inflammatory M2‐like macrophages; chronic wounds; mechanical stretch

DOI:  https://doi.org/10.1096/fj.202300586R
Res Sq. 2024 Apr 23. pii: rs.3.rs-2592196. [Epub ahead of print]

Red Blood Cell DNA Capture and Delivery Drives Host Responses During Polymicrobial Sepsis.

Long Kwan Lam, Nathan Klingensmith, Layal Sayegh, Emily Oatman, Joshua Jose, Christopher Cosgriff, Kaitlyn Eckart, John McGinnis, Piyush Ranjan, Matthew Lanza, Nadir Yehya, Nuala Meyer, Robert Dickson, Nilam Mangalmurti.

Red blood cells (RBCs), traditionally recognized for their role in transporting oxygen, play a pivotal role in the body's immune response by expressing TLR9 and scavenging excess host cell-free DNA. DNA capture by RBCs leads to accelerated RBC clearance and triggers inflammation. Whether RBCs can also acquire microbial DNA during infections is unknown. Murine RBCs acquire microbial DNA in vitro and bacterial-DNA-induced macrophage activation was augmented by WT but not TLR9-deleted RBCs. In a mouse model of polymicrobial sepsis, RBC-bound bacterial DNA was elevated in WT but not in erythroid TLR9-deleted mice. Plasma cytokine analysis revealed distinct sepsis endotypes, characterized by persistent hypothermia and hyperinflammation in the most severely affected subjects. RBC-TLR9 deletion attenuated plasma and tissue IL-6 production in the most severe endotype. Parallel findings in human subjects confirmed that RBCs from septic patients harbored more bacterial DNA compared to healthy individuals. Further analysis through 16S sequencing of RBC-bound DNA illustrated distinct microbial communities, with RBC-bound DNA composition correlating with plasma IL-6 in patients with sepsis. Collectively, these findings unveil RBCs as overlooked reservoirs and couriers of microbial DNA, capable of influencing host inflammatory responses in sepsis.

DOI: https://doi.org/10.21203/rs.3.rs-2592196/v2
Life Sci. 2024 May 11. pii: S0024-3205(24)00303-5. [Epub ahead of print]348 122713

Deciphering epigenetic regulations in the inflammatory pathways of atopic dermatitis.

Alberto José da Silva Duarte, Sabri Saeed Sanabani.

  Atopic dermatitis, commonly referred to as atopic eczema, is a persistent inflammatory skin disorder that predominantly manifests in children but may endure into adulthood. Its clinical management poses challenges due to the absence of a definitive cure, and its prevalence varies across ethnicities, genders, and geographic locations. The epigenetic landscape of AD includes changes in DNA methylation, changes in histone acetylation and methylation, and regulation by non-coding RNAs. These changes affect inflammatory and immune mechanisms, and research has identified AD-specific variations in DNA methylation, particularly in the affected epidermis. Histone modifications, including acetylation, have been associated with the disruption of skin barrier function in AD, suggesting the potential therapeutic benefit of histone deacetylase inhibitors such as belinostat. Furthermore, non-coding RNAs, particularly microRNAs and long non-coding RNAs (lncRNAs), have been implicated in modulating various cellular processes central to AD pathogenesis. Therapeutic implications in AD include the potential use of DNA methylation inhibitors and histone deacetylase inhibitors to correct aberrant methylation patterns and modulate gene expression related to immune responses and skin barrier functions. Additionally, the emerging role of lncRNAs suggests the possibility of using small interfering RNAs or antisense oligonucleotides to inhibit lncRNAs and adjust their regulatory impact on gene expression. In conclusion, the importance of epigenetic elements in AD is becoming increasingly clear as studies highlight the contribution of DNA methylation, histone modifications and, control by non-coding RNAs to the onset and progression of the disease. Understanding these epigenetic changes provides valuable insights for developing targeted therapeutic strategies.

Keywords:  Atopic dermatitis; Barrier dysfunction; Epigenetic; Inflammation; Non-coding RNAs

DOI:  https://doi.org/10.1016/j.lfs.2024.122713
Redox Biol. 2024 May 09. pii: S2213-2317(24)00165-4. [Epub ahead of print]73 103187

Central carbon metabolism exhibits unique characteristics during the handling of fungal patterns by monocyte-derived dendritic cells.

Yolanda Alvarez, Cristina Mancebo, Sara Alonso, Olimpio Montero, Nieves Fernández, Mariano Sánchez Crespo.

  Monocyte-derived dendritic cells (MDDCs) are key players in the defense against fungal infection because of their outstanding capacity for non-opsonic phagocytosis and phenotypic plasticity. Accordingly, MDDCs rewire metabolism to meet the energetic demands for microbial killing and biomass synthesis required to restore homeostasis. It has been commonplace considering the metabolic reprogramming a mimicry of the Warburg effect observed in tumor cells. However, this may be an oversimplification since the offshoots of glycolysis and the tricarboxylic acid (TCA) cycle are connected in central carbon metabolism. Zymosan, the external wall of Saccharomyces cerevisiae, contains β-glucan and α-mannan chains that engage the C-type lectin receptors dectin-1/2 and Toll-like receptors. This makes it an optimal fungal surrogate for experimental research. Using real-time bioenergetic assays and [U-13C]glucose labeling, central hubs connected to cytokine expression were identified. The pentose phosphate pathway (PPP) exhibited a more relevant capacity to yield ribose-5-phosphate than reducing equivalents of NADPH, as judged from the high levels of isotopologues showing 13C-labeling in the ribose moiety and the limited contribution of the oxidative arm of the PPP to the production of ROS by NADPH oxidases (NOX). The finding of 13C-label in the purine ring and in glutathione unveiled the contribution of serine-derived glycine to purine ring and glutathione synthesis. Serine synthesis also supported the TCA cycle. Zymosan exhausted NAD+ and ATP, consistent with intracellular consumption and/or extracellular export. Poly-ADP-ribosylated proteins detected in the nuclear fractions of MDDCs did not show major changes upon zymosan stimulation, which suggests its dependence on constitutive Fe(II)/2-oxoglutarate-dependent demethylation of 5-methylcytosine by TET translocases and/or demethylation of histone H3 lysine 27 by JMJD demethylases rather than on NOX activities. These results disclose a unique pattern of central carbon metabolism following fungal challenge, characterized by the leverage of glycolysis offshoots and an extensive recycling of NAD+ and poly(ADP-ribose).

Keywords:  Cytokines; Dendritic cells; Fungal infection; Glycolysis; Mitochondrial shuttles; Serine biosynthesis

DOI:  https://doi.org/10.1016/j.redox.2024.103187