bims-bac4me 2023-09-03 papers

bims-bac4me

Biomed News

on Microbiome and trained immunity

Issue of 2023‒09‒03
eighteen papers selected by
Chun-Chi Chang, University Hospital Zurich

A comparative study of in vitro air-liquid interface culture models of the human airway epithelium evaluating cellular heterogeneity and gene expression at single cell resolution.
Immunometabolism in the pathogenesis of asthma.
Fate-Mapping Macrophages: From Ontogeny to Functions.
Pulmonary inflammation and fibroblast immunoregulation: from bench to bedside.
Temporal relationships between Staphylococcus aureus colonization, filaggrin expression, and pediatric atopic dermatitis.
Macrophage Development and Function.
Function of reactive oxygen species in myeloid-derived suppressor cells.
Promoting mitochondrial dynamic equilibrium attenuates sepsis-induced acute lung injury by inhibiting pro-inflammatory polarization of alveolar macrophages.
Rapid and strain-specific resistance evolution of Staphylococcus aureus against inhibitory molecules secreted by Pseudomonas aeruginosa.
Isolation and Flow Cytometry Analysis of Macrophages from the Dermis.
The upper respiratory tract microbiota of healthy adults is affected by Streptococcus pneumoniae carriage, smoking habits, and contact with children.
Single-Cell Profiling of Premature Neonate Airways Reveals a Continuum of Myeloid Differentiation.
A systematic review of the clinical impact of small colony variants in patients with cystic fibrosis.
The respiratory tract microbiome, the pathogen load, and clinical interventions define severity of bacterial pneumonia.
Limosilactobacillus reuteri in immunomodulation: molecular mechanisms and potential applications.
Metagenomics and metabolomics approaches in the study of Candida albicans colonization of host niches: a framework for finding microbiome-based antifungal strategies.
Unveiling Macrophage Heterogeneity and Their Spatial Distribution Using Multiplexed Tissue Imaging.
Sepsis induces non-classic innate immune memory in granulocytes.

Respir Res. 2023 Aug 28. 24(1): 213

A comparative study of in vitro air-liquid interface culture models of the human airway epithelium evaluating cellular heterogeneity and gene expression at single cell resolution.

Rachel A Prescott, Alec P Pankow, Maren de Vries, Keaton M Crosse, Roosheel S Patel, Mark Alu, Cynthia Loomis, Victor Torres, Sergei Koralov, Ellie Ivanova, Meike Dittmann, Brad R Rosenberg.

  BACKGROUND: The airway epithelium is composed of diverse cell types with specialized functions that mediate homeostasis and protect against respiratory pathogens. Human airway epithelial (HAE) cultures at air-liquid interface are a physiologically relevant in vitro model of this heterogeneous tissue and have enabled numerous studies of airway disease. HAE cultures are classically derived from primary epithelial cells, the relatively limited passage capacity of which can limit experimental methods and study designs. BCi-NS1.1, a previously described and widely used basal cell line engineered to express hTERT, exhibits extended passage lifespan while retaining the capacity for differentiation to HAE. However, gene expression and innate immune function in BCi-NS1.1-derived versus primary-derived HAE cultures have not been fully characterized.METHODS: BCi-NS1.1-derived HAE cultures (n = 3 independent differentiations) and primary-derived HAE cultures (n = 3 distinct donors) were characterized by immunofluorescence and single cell RNA-Seq (scRNA-Seq). Innate immune functions were evaluated in response to interferon stimulation and to infection with viral and bacterial respiratory pathogens.
RESULTS: We confirm at high resolution that BCi-NS1.1- and primary-derived HAE cultures are largely similar in morphology, cell type composition, and overall gene expression patterns. While we observed cell-type specific expression differences of several interferon stimulated genes in BCi-NS1.1-derived HAE cultures, we did not observe significant differences in susceptibility to infection with influenza A virus and Staphylococcus aureus.
CONCLUSIONS: Taken together, our results further support BCi-NS1.1-derived HAE cultures as a valuable tool for the study of airway infectious disease.

Keywords:  Airway epithelium; Air–liquid interface epithelial culture; Innate immunity; Respiratory infection; Single cell transcriptomics

DOI:  https://doi.org/10.1186/s12931-023-02514-2
Immunology. 2023 Aug 31.

Immunometabolism in the pathogenesis of asthma.

Ziwen Qin, Yujuan Chen, Yue Wang, Yeyang Xu, Tingting Liu, Qian Mu, Chuanjun Huang.

  Bronchial asthma is a heterogeneous disease characterised by chronic airway inflammation. A variety of immune cells such as eosinophils, mast cells, T lymphocytes, neutrophils and airway epithelial cells are involved in the airway inflammation and airway hyperresponsiveness in asthma pathogenesis, resulting in extensive and variable reversible expiratory airflow limitation. However, the precise molecular mechanisms underlying the allergic immune responses, particularly immunometabolism, remains unclear. Studies have detected enhanced oxidative stress, and abnormal metabolic progresses of glycolysis, fatty acid and amino acid in various immune cells, inducing dysregulation of innate and adaptive immune responses in asthma pathogenesis. Immunometabolism mechanisms contain multiple signalling pathways, providing novel therapy targets for asthma. This review summarises the current knowledge on immunometabolism reprogramming in asthma pathogenesis, as well as potential therapy strategies.

Keywords:  airway hyperresponsiveness; airway inflammation; airway remodelling; asthma; immune cell; immune response; immunometabolism; metabolic reprogramming

DOI:  https://doi.org/10.1111/imm.13688
Methods Mol Biol. 2024 ;2713 11-43

Fate-Mapping Macrophages: From Ontogeny to Functions.

Anna Ahlback, Rebecca Gentek.

  Macrophages are vital to the physiological function of most tissues, but also contribute to disease through a multitude of pathological roles. They are thus highly plastic and heterogeneous. It is now well recognized that macrophages develop from several distinct progenitors from embryogenesis onwards and extending throughout life. Tissue-resident macrophages largely originate from embryonic sources and in many cases self-maintain independently without monocyte input. However, in certain tissues, monocyte-derived macrophages replace these over time or as a result of tissue injury and inflammation. This additional layer of heterogeneity has introduced many questions regarding the influence of origin on fate and function of macrophages in health and disease. To comprehensively address these questions, appropriate methods of tracing macrophage ontogeny are required. This chapter explores why ontogeny is of vital importance in macrophage biology and how to delineate macrophage populations by origin through genetic fate mapping. First, we summarize the current view of macrophage ontogeny and briefly discuss how origin may influence macrophage function in homeostasis and pathology. We go on to make the case for genetic fate mapping as the gold standard and briefly review different fate-mapping models. We then put forward our recommendations for fate-mapping strategies best suited to answer specific research questions and finally discuss the strengths and limitations of currently available models.

Keywords:  Erythro-myeloid progenitors (EMPs); Fate mapping; Hematopoietic stem cells (HSCs); Macrophages; Monocytes

DOI:  https://doi.org/10.1007/978-1-0716-3437-0_2
J Clin Invest. 2023 Sep 01. pii: e170499. [Epub ahead of print]133(17):

Pulmonary inflammation and fibroblast immunoregulation: from bench to bedside.

Mohamed A Ghonim, David F Boyd, Tim Flerlage, Paul G Thomas.

In recent years, there has been an explosion of interest in how fibroblasts initiate, sustain, and resolve inflammation across disease states. Fibroblasts contain heterogeneous subsets with diverse functionality. The phenotypes of these populations vary depending on their spatial distribution within the tissue and the immunopathologic cues contributing to disease progression. In addition to their roles in structurally supporting organs and remodeling tissue, fibroblasts mediate critical interactions with diverse immune cells. These interactions have important implications for defining mechanisms of disease and identifying potential therapeutic targets. Fibroblasts in the respiratory tract, in particular, determine the severity and outcome of numerous acute and chronic lung diseases, including asthma, chronic obstructive pulmonary disease, acute respiratory distress syndrome, and idiopathic pulmonary fibrosis. Here, we review recent studies defining the spatiotemporal identity of the lung-derived fibroblasts and the mechanisms by which these subsets regulate immune responses to insult exposures and highlight past, current, and future therapeutic targets with relevance to fibroblast biology in the context of acute and chronic human respiratory diseases. This perspective highlights the importance of tissue context in defining fibroblast-immune crosstalk and paves the way for identifying therapeutic approaches to benefit patients with acute and chronic pulmonary disorders.

DOI: https://doi.org/10.1172/JCI170499
Allergy. 2023 Aug 31.

Temporal relationships between Staphylococcus aureus colonization, filaggrin expression, and pediatric atopic dermatitis.

Arya Dahal, Wan Chi Chang, Cassandra Almasri, Elisabet Johansson, Makenna Hurd, Veronica Velasquez, Brittany Grashel, Daniel Spagna, Seth Jenkins, David Morgan, Latha Satish, Lisa J Martin, Jocelyn M Biagini, Gurjit K Khurana Hershey.

  BACKGROUND: Atopic dermatitis (AD) is characterized by Staphylococcus aureus (S. aureus) colonization. Longitudinal early life data delineating relationships of S. aureus colonization, barrier function, and AD outcomes are lacking. We define longitudinal S. aureus endotypes and AD pathogenesis in early life.METHODS: We defined longitudinal S. aureus skin colonization phenotypes across two annual visits (non-colonized: V1- V2- , early transient: V1+ V2- , late-onset: V1- V2+ , persistent: V1+ V2+ ) in the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children cohort. We analyzed AD severity, sensitization, and skin barrier function across phenotypes, and performed mediation analyses between colonization and FLG expression.
RESULTS: Persistent S. aureus colonization was associated with increased SCORAD at V1 (33.5 vs. 19.0, p = .004) and V2 (40.1 vs.16.9, p < .001), and lower non-lesional (NL) FLG at V2 (1.77 vs. 4.09, p = .029) compared to the non-colonized phenotype, with early transient and late-onset colonization as intermediate phenotypes. Children colonized at V2 demonstrated a decrease in NL-FLG expression from V1 to V2 compared to those non-colonized at V2 (p = .0012), who maintained expression. This effect remained significant even after adjusting for V1 colonization and SCORAD (p = .011).
CONCLUSIONS: Our findings are the first to present longitudinal quantitative FLG expression and S. aureus skin colonization in early life and suggest that a decrease in NL-FLG drives later colonization. Hence, therapies to maintain NL-FLG expression may prevent S. aureus colonization. Further, a longitudinal AD endotype of persistent colonization is characterized by increased AD severity, sensitization, and decreasing NL-FLG.

Keywords:   Staphylococcus aureus ; atopic dermatitis; filaggrin expression; longitudinal colonization; mediation analysis

DOI:  https://doi.org/10.1111/all.15871
Methods Mol Biol. 2024 ;2713 1-9

Macrophage Development and Function.

Nikola Makdissi.

  Macrophages were first described over a hundred years ago. Throughout the years, they were shown to be essential players in their tissue-specific environment, performing various functions during homeostatic and disease conditions. Recent reports shed more light on their ontogeny as long-lived, self-maintained cells with embryonic origin in most tissues. They populate the different tissues early during development, where they help to establish and maintain homeostasis. In this chapter, the history of macrophages is discussed. Furthermore, macrophage ontogeny and core functions in the different tissues are described.

Keywords:  Hematopoietic waves; Macrophage ontogeny; Monocytes; Phagocytes; Tissue-resident macrophages

DOI:  https://doi.org/10.1007/978-1-0716-3437-0_1
Front Immunol. 2023 ;14 1226443

Function of reactive oxygen species in myeloid-derived suppressor cells.

Jiaojiao Huang, Yue Zhao, Kexin Zhao, Kai Yin, Shengjun Wang.

  Myeloid-derived suppressor cells (MDSCs) are a heterogeneous myeloid cell population and serve as a vital contributor to the tumor microenvironment. Reactive oxygen species (ROS) are byproducts of aerobic respiration and are involved in regulating normal biological activities and disease progression. MDSCs can produce ROS to fulfill their immunosuppressive activity and eliminate excessive ROS to survive comfily through the redox system. This review focuses on how MDSCs survive and function in high levels of ROS and summarizes immunotherapy targeting ROS in MDSCs. The distinctive role of ROS in MDSCs will inspire us to widely apply the blocked oxidative stress strategy in targeting MDSC therapy to future clinical therapeutics.

Keywords:  MDSCs; ROS; immunotherapy; tumor; tumor micro environment (TME)

DOI:  https://doi.org/10.3389/fimmu.2023.1226443
Shock. 2023 Aug 22.

Promoting mitochondrial dynamic equilibrium attenuates sepsis-induced acute lung injury by inhibiting pro-inflammatory polarization of alveolar macrophages.

Maomao Sun, Zhenhua Zeng, Gege Xu, Sheng An, Zhiya Deng, Ran Cheng, Yi Yao, Junjie Wu, Hongbin Hu, Qiaobing Huang, Jie Wu.

ABSTRACT: Sepsis-induced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by widespread pulmonary inflammation and immune response, in which pro-inflammatory polarization of alveolar macrophages (AMs) plays an important role. Mitochondria are the key intracellular signaling platforms regulating immune cell responses. Moreover, accumulating evidence suggests that the mitochondrial dynamics of macrophages are imbalanced in sepsis and severe ALI/ARDS. However, the functional significance of mitochondrial dynamics of AMs in septic ALI/ARDS remains largely unknown, and whether it regulates the polarized phenotype of AMs is also unclear. Here, we demonstrated that the mitochondrial dynamics of AMs are imbalanced, manifested by impaired mitochondrial fusion, increased fission and mitochondrial cristae remodeling, both in septic models and ARDS patients. However, suppressing excessive mitochondrial fission with Mdivi-1 or promoting mitochondrial fusion with PM1 to maintain mitochondrial dynamic equilibrium in AMs could inhibit the polarization of AMs into pro-inflammatory phenotype and attenuate sepsis-induced ALI. These data suggest that mitochondrial dynamic imbalance mediates altered polarization of AMs and exacerbates sepsis-induced ALI. This study provides new insights into the underlying mechanisms of sepsis-induced ALI, suggesting the possibility of identifying future drug targets from the perspective of mitochondrial dynamics in AMs.

DOI: https://doi.org/10.1097/SHK.0000000000002206
mBio. 2023 Aug 30. e0315322

Rapid and strain-specific resistance evolution of Staphylococcus aureus against inhibitory molecules secreted by Pseudomonas aeruginosa.

Selina Niggli, Lukas Schwyter, Lucy Poveda, Jonas Grossmann, Rolf Kümmerli.

  Pseudomonas aeruginosa and Staphylococcus aureus frequently occur together in polymicrobial infections, and there is evidence that their interactions negatively affect disease outcome in patients. At the molecular level, interactions between the two bacterial species are well-described, with P. aeruginosa usually being the dominant species suppressing S. aureus through a variety of inhibitory molecules. However, in chronic infections the two species interact over prolonged periods of time, and S. aureus might be able to evolve resistance against inhibitory molecules deployed by P. aeruginosa. Here, we used experimental evolution to test this hypothesis by exposing three different S. aureus strains (Cowan I, 6850, and JE2) to the growth-inhibitory supernatant of P. aeruginosa PAO1 over 30 days. Prior to evolution, we found that S. aureus strains were inhibited by secreted compounds regulatorily controlled by the Pseudomonas quinolone signal quorum-sensing system. Following evolution, inhibitory effects were significantly attenuated, and we observed that adaptations were S. aureus strain specific and involved the upregulation of virulence traits such as staphyloxanthin production and the formation of small colony variants. At the genetic level, mutations in membrane transporters (known to be involved in antibacterial uptake) were the most frequent evolutionary targets. Our work indicates that adaptations of S. aureus to P. aeruginosa occurs rapidly and affect both virulence trait expression and membrane transporter functionality. Thus, pathogen evolution could promote species co-existence and complicate treatment options in infections. IMPORTANCE Polymicrobial infections are common. In chronic infections, the different pathogens may repeatedly interact, which could spur evolutionary dynamics with pathogens adapting to one another. Here, we explore the potential of Staphylococcus aureus to adapt to its competitor Pseudomonas aeruginosa. These two pathogens frequently co-occur, and P. aeruginosa is seen as the dominant species being able to displace S. aureus. We studied three different S. aureus strains and found that all became quickly resistant to inhibitory compounds secreted by P. aeruginosa. Our experimental evolution revealed strains-specific adaptations with three main factors contributing to resistance evolution: (i) overproduction of staphyloxanthin, a molecule protecting from oxidative stress; (ii) the formation of small colony variants also protecting from oxidative stress; and (iii) alterations of membrane transporters possibly reducing toxin uptake. Our results show that species interactions can change over time potentially favoring species co-existence, which in turn could affect disease progression and treatment options.

Keywords:  competition; microbe-microbe interactions; nosocomial pathogen; pathogen evolution; polymicrobial infections; resistance evolution

DOI:  https://doi.org/10.1128/mbio.03153-22
Methods Mol Biol. 2024 ;2713 159-169

Isolation and Flow Cytometry Analysis of Macrophages from the Dermis.

Aaron James Forde, Julia Kolter.

  The dermis contains a dense network of tissue macrophages, which contribute to tissue homeostasis, inflammation, and pathogen clearance. Dermal macrophages are partly replenished by circulating monocytes, which fuel the resident population, especially in case of tissue damage or inflammation. The complexity of the tissue, containing blood and lymphoid vessels, hair bulbs, sebaceous glands, and peripheral nerves, allows for the development of distinct macrophages populations. In steady state, discrete subtypes can be distinguished due to their surface marker expression and localization within the dermis. In this chapter, we describe how to extract dermal macrophages from the skin and highlight different gating strategies to identify monocyte and macrophage populations.

Keywords:  Dermis; Isolation; Macrophages; Monocytes; Mononuclear Phagocytes; Skin

DOI:  https://doi.org/10.1007/978-1-0716-3437-0_11
Microbiome. 2023 Sep 02. 11(1): 199

The upper respiratory tract microbiota of healthy adults is affected by Streptococcus pneumoniae carriage, smoking habits, and contact with children.

A Cristina Paulo, João Lança, Sónia T Almeida, Markus Hilty, Raquel Sá-Leão.

  BACKGROUND: The microbiota of the upper respiratory tract is increasingly recognized as a gatekeeper of respiratory health. Despite this, the microbiota of healthy adults remains understudied. To address this gap, we investigated the composition of the nasopharyngeal and oropharyngeal microbiota of healthy adults, focusing on the effect of Streptococcus pneumoniae carriage, smoking habits, and contact with children.RESULTS: Differential abundance analysis indicated that the microbiota of the oropharynx was significantly different from that of the nasopharynx (P < 0.001) and highly discriminated by a balance between the classes Negativicutes and Bacilli (AUC of 0.979). Moreover, the oropharynx was associated with a more homogeneous microbiota across individuals, with just two vs. five clusters identified in the nasopharynx. We observed a shift in the nasopharyngeal microbiota of carriers vs. noncarriers with an increased relative abundance of Streptococcus, which summed up to 30% vs. 10% in noncarriers and was not mirrored in the oropharynx. The oropharyngeal microbiota of smokers had a lower diversity than the microbiota of nonsmokers, while no differences were observed in the nasopharyngeal microbiota. In particular, the microbiota of smokers, compared with nonsmokers, was enriched (on average 16-fold) in potential pathogenic taxa involved in periodontal diseases of the genera Bacillus and Burkholderia previously identified in metagenomic studies of cigarettes. The microbiota of adults with contact with children resembled the microbiota of children. Specifically, the nasopharyngeal microbiota of these adults had, on average, an eightfold increase in relative abundance in Streptococcus sp., Moraxella catarrhalis, and Haemophilus influenzae, pathobionts known to colonize the children's upper respiratory tract, and a fourfold decrease in Staphylococcus aureus and Staphylococcus lugdunensis.
CONCLUSIONS: Our study showed that, in adults, the presence of S. pneumoniae in the nasopharynx is associated with a shift in the microbiota and dominance of the Streptococcus genus. Furthermore, we observed that smoking habits are associated with an increase in bacterial genera commonly linked to periodontal diseases. Interestingly, our research also revealed that adults who have regular contact with children have a microbiota enriched in pathobionts frequently carried by children. These findings collectively contribute to a deeper understanding of how various factors influence the upper respiratory tract microbiota in adults. Video Abstract.

Keywords:  Healthy adults; Microbiota; Nasopharynx; Oropharynx; Streptococcus pneumoniae

DOI:  https://doi.org/10.1186/s40168-023-01640-9
Am J Respir Cell Mol Biol. 2023 Aug 29.

Single-Cell Profiling of Premature Neonate Airways Reveals a Continuum of Myeloid Differentiation.

Holly Welfley, Ranjit Kylat, Nahla Zaghloul, Marilyn Halonen, Fernando D Martinez, Mohamed Ahmed, Darren A Cusanovich.

  Single-cell genomic technologies hold great potential to advance our understanding of lung development and disease. A major limitation lies in accessing intact cells from primary lung tissues for profiling human airway health. Sampling methods, such as endotracheal aspirates, that are compatible with clinical interventions could enable longitudinal studies, the enrollment of large cohorts, and the development of novel diagnostics. To explore single-cell RNA-seq (scRNA-seq) profiling of the cell types present at birth in the airway lumen of extremely premature neonates (<28 weeks gestation). We isolated cells from endotracheal aspirates collected from intubated neonates within the first hour after birth. We generated data on 10 subjects, providing a rich view of airway luminal biology at a critical developmental period. Our results show that cells present in the airways of premature neonates primarily represent a continuum of myeloid differentiation, including fetal monocytes (25% of total), intermediate myeloid populations (48%), and macrophages (2.6%). Applying trajectory analysis to the myeloid populations, we identified two trajectories consistent with the developmental stages of interstitial and alveolar macrophages, as well as a third trajectory presenting an alternative pathway bridging the distinct macrophage precursors. The three trajectories share many dynamic genes (5,451), but also have distinct transcriptional changes (259 alveolar-specific, 666 interstitial-specific, and 285 bridging-specific). Overall, our results define cells isolated within the so-called "golden hour of birth" in extremely premature neonate airways representing complex lung biology and can be utilized in studies of human development and disease.

Keywords:  Genomics; Lung; Newborn

DOI:  https://doi.org/10.1165/rcmb.2022-0293OC
BMC Pulm Med. 2023 Sep 01. 23(1): 323

A systematic review of the clinical impact of small colony variants in patients with cystic fibrosis.

Harrigan Ryan, Emma Ballard, Rebecca E Stockwell, Christine Duplancic, Rachel M Thomson, Kimberley Smith, Scott C Bell.

  BACKGROUND: Cystic fibrosis (CF) is a life-limiting disorder that is characterised by respiratory tract inflammation that is mediated by a range of microbial pathogens. Small colony variants (SCVs) of common respiratory pathogens are being increasingly recognised in CF. The aim of this systematic review is to investigate the prevalence of SCVs, clinical characteristics and health outcomes for patients with CF, and laboratory diagnostic features of SCVs compared to non-small colony variants (NCVs) for a range of Gram-positive and Gram-negative respiratory pathogens.METHODS: A literature search was conducted (PubMed, Web of Science, Embase and Scopus) in April 2020 to identify articles of interest. Data pertaining to demographic characteristics of participants, diagnostic criteria of SCVs, SCV prevalence and impact on lung function were extracted from included studies for analysis.
RESULTS: Twenty-five of 673 studies were included in the systematic review. Individuals infected with SCVs of Staphylococcus aureus (S. aureus) were more likely to have had prior use of the broad-spectrum antibiotic trimethoprim sulfamethoxazole (p < 0.001), and the prevalence of SCVs in patients infected with S. aureus was estimated to be 19.3% (95% CI: 13.5% to 25.9%). Additionally, patients infected with SCVs of Gram-negative and Gram-positive pathogens were identified to have a lower forced expiratory volume in one second percentage predicted (-16.8, 95% CI: -23.2 to -10.4) than those infected by NCVs. Gram-positive SCVs were commonly described as small and non-haemolytic, grown on Mannitol salt or blood agar for 24 h at 35°C and confirmed using tube coagulase testing.
CONCLUSION: The findings of this systematic review demonstrate that SCVs of S. aureus have a high prevalence in the CF community, and that the occurrence of SCVs in Gram-positive and Gram-negative pathogens is linked to poorer respiratory function. Further investigation is necessary to determine the effect of infection by SCVs on the CF population.

Keywords:  Clinical impact; Cystic fibrosis; Prevalence; Small colony variants

DOI:  https://doi.org/10.1186/s12890-023-02611-4
Cell Rep Med. 2023 Aug 17. pii: S2666-3791(23)00320-8. [Epub ahead of print] 101167

The respiratory tract microbiome, the pathogen load, and clinical interventions define severity of bacterial pneumonia.

Ana Elena Pérez-Cobas, Christophe Ginevra, Christophe Rusniok, Sophie Jarraud, Carmen Buchrieser.

  Bacterial pneumonia is a considerable problem worldwide. Here, we follow the inter-kingdom respiratory tract microbiome (RTM) of a unique cohort of 38 hospitalized patients (n = 97 samples) with pneumonia caused by Legionella pneumophila. The RTM composition is characterized by diversity drops early in hospitalization and ecological species replacement. RTMs with the highest bacterial and fungal loads show low diversity and pathogen enrichment, suggesting high biomass as a biomarker for secondary and/or co-infections. The RTM structure is defined by a "commensal" cluster associated with a healthy RTM and a "pathogen" enriched one, suggesting that the cluster equilibrium drives the microbiome to recovery or dysbiosis. Legionella biomass correlates with disease severity and co-morbidities, while clinical interventions influence the RTM dynamics. Fungi, archaea, and protozoa seem to contribute to progress of pneumonia. Thus, the interplay of the RTM equilibrium, the pathogen load dynamics, and clinical interventions play a critical role in patient recovery.

Keywords:  Legionella pneumophila; biomass; microbial ecology; pneumonia; respiratory tract microbiome; severity

DOI:  https://doi.org/10.1016/j.xcrm.2023.101167
Front Immunol. 2023 ;14 1228754

Limosilactobacillus reuteri in immunomodulation: molecular mechanisms and potential applications.

Zichen Luo, Ailing Chen, Anni Xie, Xueying Liu, Shanyu Jiang, Renqiang Yu.

  Frequent use of hormones and drugs may be associated with side-effects. Recent studies have shown that probiotics have effects on the prevention and treatment of immune-related diseases. Limosilactobacillus reuteri (L. reuteri) had regulatory effects on intestinal microbiota, host epithelial cells, immune cells, cytokines, antibodies (Ab), toll-like receptors (TLRs), tryptophan (Try) metabolism, antioxidant enzymes, and expression of related genes, and exhibits antibacterial and anti-inflammatory effects, leading to alleviation of disease symptoms. Although the specific composition of the cell-free supernatant (CFS) of L. reuteri has not been clarified, its efficacy in animal models has drawn increased attention to its potential use. This review summarizes the effects of L. reuteri on intestinal flora and immune regulation, and discusses the feasibility of its application in atopic dermatitis (AD), asthma, necrotizing enterocolitis (NEC), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS), and provides insights for the prevention and treatment of immune-related diseases.

Keywords:  Limosilactobacillus reuteri; asthma; atopic dermatitis (AD); immune system disease; multiple sclerosis; necrotizing enterocolitis (NEC); rheumatoid arthritis; systemic lupus erythematosus (SLE)

DOI:  https://doi.org/10.3389/fimmu.2023.1228754
Trends Microbiol. 2023 Aug 30. pii: S0966-842X(23)00231-7. [Epub ahead of print]

Metagenomics and metabolomics approaches in the study of Candida albicans colonization of host niches: a framework for finding microbiome-based antifungal strategies.

Margot Delavy, Natacha Sertour, Christophe d'Enfert, Marie-Elisabeth Bougnoux.

  In silico and experimental approaches have allowed an ever-growing understanding of the interactions within the microbiota. For instance, recently acquired data have increased knowledge of the mechanisms that support, in the gut and vaginal microbiota, the resistance to colonization by Candida albicans, an opportunistic fungal pathogen whose overgrowth can initiate severe infections in immunocompromised patients. Here, we review how bacteria from the microbiota interact with C. albicans. We show how recent OMICs-based pipelines, using metagenomics and/or metabolomics, have identified bacterial species and metabolites modulating C. albicans growth. We finally discuss how the combined use of cutting-edge OMICs-based and experimental approaches could provide new means to control C. albicans overgrowth within the microbiota and prevent its consequences.

Keywords:  Candida albicans; OMICs approaches; microbial signatures; microbiota

DOI:  https://doi.org/10.1016/j.tim.2023.08.002
Methods Mol Biol. 2024 ;2713 281-296

Unveiling Macrophage Heterogeneity and Their Spatial Distribution Using Multiplexed Tissue Imaging.

David Alejandro Bejarano, Andreas Schlitzer.

  Macrophages display a high degree of phenotypic diversity and plasticity, which is influenced by their location within the tissue microenvironment. Co-Detection by Indexing (CODEX), a multiplexed imaging technique, allows the simultaneous detection of multiple membrane and cellular markers that enable the accurate identification of tissue-resident hematopoietic and non-hematopoietic cells, while conferring spatial information at a single-cell level. Here we describe the use of CODEX to visualize the phenotypic and spatial heterogeneity of murine tissue-resident macrophages in several organs, and a pipeline to characterize their cellular microenvironments and interactions.

Keywords:  Co-Detection by Indexing (CODEX); Macrophage cellular neighborhoods; Macrophage heterogeneity; Macrophage localization; Multiplexed imaging; Spatial proteomics

DOI:  https://doi.org/10.1007/978-1-0716-3437-0_19
Cell Rep. 2023 Aug 28. pii: S2211-1247(23)01055-0. [Epub ahead of print]42(9): 113044

Sepsis induces non-classic innate immune memory in granulocytes.

Beibei Wang, Liuluan Zhu, Bei Jia, Chenchen Zhao, Ju Zhang, Fangyuan Li, Jiarui Li, Nan Ding, Can Zhang, Yu Hao, Shuai Tong, Jiajia Wang, Guoli Li, Yang Fan, Henghui Zhang, Rui Li, Juan Du, Yaxian Kong, Yue Zhang, Xiaoyu Yang, Junyan Han, Zhengya Yu, Zhongtao Du, Hong Zheng, Christian Kosan, Ang Li, Chen Chen, Yaluan Ma, Hui Zeng.

  Secondary infection in patients with sepsis triggers a new wave of inflammatory response, which aggravates organ injury and increases mortality. Trained immunity boosts a potent and nonspecific response to the secondary challenge and has been considered beneficial for the host. Here, using a murine model of polymicrobial infection, we find that the primary infection reprograms granulocytes to boost enhanced inflammatory responses to the secondary infection, including the excessive production of inflammatory cytokines, respiratory burst, and augmented phagocytosis capacity. However, these reprogramed granulocytes exhibit "non-classic" characteristics of innate immune memory. Two mechanisms are independently involved in the innate immune memory of granulocytes: a metabolic shift in favor of glycolysis and fatty acid synthesis and chromatin remodeling leading to the transcriptional inactivity of genes encoding inhibitors of TLR4-initiated signaling pathways. Counteracting the deleterious effects of stressed granulocytes on anti-infection immunity might provide a strategy to fight secondary infections during sepsis.

Keywords:  CP: Immunology; granulocyte; immune memory; secondary infection; sepsis

DOI:  https://doi.org/10.1016/j.celrep.2023.113044