bims-bac4me 2023-04-02 papers

bims-bac4me

Biomed News

on Microbiome and trained immunity

Issue of 2023–04–02
thirteen papers selected by
Chun-Chi Chang, University Hospital Zurich

Training vs. Tolerance: The Yin/Yang of the Innate Immune System.
Transmission of stimulus-induced epigenetic changes through cell division is coupled to continuous transcription factor activity.
The macrophage polarization in inflammatory dermatosis and its potential drug candidates.
Trained immunity: A "new" weapon in the fight against infectious diseases.
MSF Enhances Human Antimicrobial Peptide β-Defensin (HBD2 and HBD3) Expression and Attenuates Inflammation via the NF-κB and p38 Signaling Pathways.
Microbiota-derived short-chain fatty acids and modulation of host-derived peptides formation: Focused on host defense peptides.
The microbiome as a major function of the gastrointestinal tract and its implication in micronutrient metabolism and chronic diseases.
Monocytes can proliferate in vacant niches before differentiation into macrophages.
Microbial metabolites and immunotherapy: Basic rationale and clinical indications.
Metabolic regulation of dendritic cell activation and immune function during inflammation.
Arresting microbiome development limits immune system maturation and resistance to infection in mice.
Lung microbiome: an emerging player in lung cancer pathogenesis and progression.
The diverse roles of macrophages in metabolic inflammation and its resolution.

Biomedicines. 2023 Mar 02. pii: 766. [Epub ahead of print]11(3):

Training vs. Tolerance: The Yin/Yang of the Innate Immune System.

Trim Lajqi, Natascha Köstlin-Gille, Reinhard Bauer, Sotirios G Zarogiannis, Esra Lajqi, Valdrina Ajeti, Stefanie Dietz, Simon A Kranig, Jessica Rühle, Ardian Demaj, Janine Hebel, Maria Bartosova, David Frommhold, Hannes Hudalla, Christian Gille.

  For almost nearly a century, memory functions have been attributed only to acquired immune cells. Lately, this paradigm has been challenged by an increasing number of studies revealing that innate immune cells are capable of exhibiting memory-like features resulting in increased responsiveness to subsequent challenges, a process known as trained immunity (known also as innate memory). In contrast, the refractory state of endotoxin tolerance has been defined as an immunosuppressive state of myeloid cells portrayed by a significant reduction in the inflammatory capacity. Both training as well tolerance as adaptive features are reported to be accompanied by epigenetic and metabolic alterations occurring in cells. While training conveys proper protection against secondary infections, the induction of endotoxin tolerance promotes repairing mechanisms in the cells. Consequently, the inappropriate induction of these adaptive cues may trigger maladaptive effects, promoting an increased susceptibility to secondary infections-tolerance, or contribute to the progression of the inflammatory disorder-trained immunity. This review aims at the discussion of these opposing manners of innate immune and non-immune cells, describing the molecular, metabolic and epigenetic mechanisms involved and interpreting the clinical implications in various inflammatory pathologies.

Keywords:  DAMPs; PAMPs; diseases; dose; epigenetic; inflammatory; metabolic; signaling; tolerance; trained immunity

DOI:  https://doi.org/10.3390/biomedicines11030766
Front Immunol. 2023 ;14 1129577

Transmission of stimulus-induced epigenetic changes through cell division is coupled to continuous transcription factor activity.

Sarah Sun, Raúl Aguirre-Gamboa, Luis B Barreiro.

  Trained immunity, or innate immune memory, has been attributed to the long-term retention of stimulus-induced histone post-translational modifications (PTMs) following clearance of the initial stimulus. Yet, it remains unknown how this epigenetic memory can persist for months in dividing cells given the lack of any known mechanism for stimulus-induced histone PTMs to be directly copied from parent to daughter strand during DNA replication. Here, using time course RNA-seq, ChIP-seq, and infection assays, we find that trained macrophages are transcriptionally, epigenetically, and functionally re-programmed for at least 14 cell divisions after stimulus washout. However, the epigenetic changes observed after multiple rounds of cell division do not result from the self-sustained propagation of stimulus-induced epigenetic changes through cell division. Instead, long-lasting epigenetic differences between trained and non-trained cells are always coupled with changes in transcription factor (TF) activity, emphasizing the central role played by TFs, and gene expression changes more broadly, in driving the transmission of stimulus-induced epigenetic changes across cell divisions.

Keywords:  epigenetics; histone modifications; immunogenomics; innate immune memory; macrophages; trained immunity

DOI:  https://doi.org/10.3389/fimmu.2023.1129577
Biomed Pharmacother. 2023 May;pii: S0753-3322(23)00257-3. [Epub ahead of print]161 114469

The macrophage polarization in inflammatory dermatosis and its potential drug candidates.

Qingru Sun, Shiyu Hu, Zhaohuan Lou, Jianli Gao.

  Inflammatory dermatosis is characterized by persistent inflammatory infiltration and hard repair of diseased skin. As a member of the human innate immune cells, macrophages usually show different phenotypes in different diseases. The macrophage phenotype (M1/M2) imbalance caused by the increase of M1 macrophages or the decrease of M2 macrophages is common in inflammatory dermatosis. In recent years, with the deepening research on inflammatory skin diseases, more and more natural medicines/traditional Chinese medicines (TCMs), represented by Shikonin and Angelica Dahurica, have shown their therapeutic effects by affecting the polarization of macrophages. This review introduced macrophage polarization in different inflammatory dermatosis, such as psoriasis. Then summarized the natural medicines/TCMs that have potential therapeutic effects so far and introduced their mechanisms of action and the proteins/signal pathways involved. We found that the TCMs with therapeutic effects listed in this review are closely related to the theory of five flavors and four properties of Chinese medicinal, and most of them are bitter, acrid and sweet. Bitter TCMs have antipyretic, anti-inflammatory and antibacterial effects, which may improve the persistent inflammation of M1 macrophage infiltration. Acrid TCMs have the effect of promoting blood circulation, while sweet TCMs have the effect of nourishing. These 2 flavors may accelerate the repair of skin lesions of inflammatory dermatosis by affecting M2 macrophages. In conclusion, we hope to provide sufficient knowledge for natural medicine research and the development of inflammatory dermatosis related to macrophage phenotype imbalance.

Keywords:  Inflammatory dermatosis; M1; M2; Macrophage polarization; Natural medicine; Traditional Chinese medicine

DOI:  https://doi.org/10.1016/j.biopha.2023.114469
Front Immunol. 2023 ;14 1147476

Trained immunity: A "new" weapon in the fight against infectious diseases.

Amy Dagenais, Carlos Villalba-Guerrero, Martin Olivier.

  Innate immune cells can potentiate the response to reinfection through an innate form of immunological memory known as trained immunity. The potential of this fast-acting, nonspecific memory compared to traditional adaptive immunological memory in prophylaxis and therapy has been a topic of great interest in many fields, including infectious diseases. Amidst the rise of antimicrobial resistance and climate change-two major threats to global health-, harnessing the advantages of trained immunity compared to traditional forms of prophylaxis and therapy could be game-changing. Here, we present recent works bridging trained immunity and infectious disease that raise important discoveries, questions, concerns, and novel avenues for the modulation of trained immunity in practice. By exploring the progress in bacterial, viral, fungal, and parasitic diseases, we equally highlight future directions with a focus on particularly problematic and/or understudied pathogens.

Keywords:  host-pathogen interactions; infectious diseases; innate immune response; innate immunological memory; myeloid cells; tolerance; trained immunity; vaccines

DOI:  https://doi.org/10.3389/fimmu.2023.1147476
Molecules. 2023 Mar 18. pii: 2744. [Epub ahead of print]28(6):

MSF Enhances Human Antimicrobial Peptide β-Defensin (HBD2 and HBD3) Expression and Attenuates Inflammation via the NF-κB and p38 Signaling Pathways.

Anh-Thu Nguyen, Minho Kim, Ye-Eun Kim, Hangeun Kim, Sanghyun Lee, Yunji Lee, Ki-Young Kim.

  Both defensin and inflammation are part of the human innate immune system that responds rapidly to pathogens. The combination of defensins with pro- or anti-inflammatory effects can be a potential research direction for the treatment of infection by pathogens. This study aimed to identify whether MSF (Miracle Synergy material made using Filipendula glaberrima), a probiotic lysate of Filipendula glaberrima extracts fermented with Lactiplantibacillus plantarum K8, activates the expression of human β-defensin (HBD2 and HBD3) to protect the host against pathogens and inhibit inflammation caused by S. aureus, in vitro with Western blot analysis, qRT-PCR and in vivo studies with a mouse model were used to evaluate the effects of MSF. The MSF treatment induced HBD2 and HBD3 expression via the p38 and NF-κB pathways. Furthermore, MSF treatment significantly reduced the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-8), also through p38 and NF-κB in S. aureus-induced inflammatory condition. MSF treatment remarkably reduced erythema in mice ears caused by the injection of S. aureus, while K8 lysate treatment did not initiate a strong recovery. Taken together, MSF induced the expression of HBD2 and HDB3 and activated anti-inflammatory activity more than the probiotic lysates of L. plantarum K8. These findings show that MSF is a potential defensin inducer and anti-inflammatory agent.

Keywords:  F. glaberrima Nakai; L. plantarum K8; MSF; anti-inflammation; defensin

DOI:  https://doi.org/10.3390/molecules28062744
Biomed Pharmacother. 2023 Mar 27. pii: S0753-3322(23)00374-8. [Epub ahead of print]162 114586

Microbiota-derived short-chain fatty acids and modulation of host-derived peptides formation: Focused on host defense peptides.

Tianzhou Liu, Zhen Sun, Zecheng Yang, Xiaofang Qiao.

  The byproducts of bacterial fermentation known as short-chain fatty acids (SCFAs) are chemically comprised of a carboxylic acid component and a short hydrocarbon chain. Recent investigations have demonstrated that SCFAs can affect intestinal immunity by inducing endogenous host defense peptides (HDPs) and their beneficial effects on barrier integrity, gut health, energy supply, and inflammation. HDPs, which include defensins, cathelicidins, and C-type lectins, perform a significant function in innate immunity in gastrointestinal mucosal membranes. SCFAs have been demonstrated to stimulate HDP synthesis by intestinal epithelial cells via interactions with G protein-coupled receptor 43 (GPR43), activation of the Jun N-terminal kinase (JNK) and Mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways, and the cell growth pathways. Furthermore, SCFA butyrate has been demonstrated to enhance the number of HDPs released from macrophages. SCFAs promote monocyte-to-macrophage development and stimulate HDP synthesis in macrophages by inhibiting histone deacetylase (HDAC). Understanding the etiology of many common disorders might be facilitated by studies into the function of microbial metabolites, such as SCFAs, in the molecular regulatory processes of immune responses (e.g., HDP production). This review will focus on the current knowledge of the role and mechanism of microbiota-derived SCFAs in influencing the synthesis of host-derived peptides, particularly HDPs.

Keywords:  Cathelicidins; Defensins; GPCRs; HDAC; HDPs; SCFAs

DOI:  https://doi.org/10.1016/j.biopha.2023.114586
Nutr Res. 2023 Mar 04. pii: S0271-5317(23)00014-3. [Epub ahead of print]112 30-45

The microbiome as a major function of the gastrointestinal tract and its implication in micronutrient metabolism and chronic diseases.

Dingbo Lin, Denis M Medeiros.

  The composition and function of microbes harbored in the human gastrointestinal lumen have been underestimated for centuries because of the underdevelopment of nucleotide sequencing techniques and the lack of humanized gnotobiotic models. Now, we appreciate that the gut microbiome is an integral part of the human body and exerts considerable roles in host health and diseases. Dietary factors can induce changes in the microbial community composition, metabolism, and function, thereby altering the host immune response, and consequently, may influence disease risks. An imbalance of gut microbiome homeostasis (i.e., dysbiosis) has been linked to several chronic diseases, such as inflammatory bowel diseases, obesity, and diabetes. Remarkable progress has recently been made in better understanding the extent to which the influence of the diet-microbiota interaction on host health outcomes in both animal models and human participants. However, the exact causality of the gut microbiome on the development of diseases is still controversial. In this review, we will briefly describe the general structure and function of the intestine and the process of nutrient absorption in humans. This is followed by a summarization of the recent updates on interactions between gut microbiota and individual micronutrients, including carotenoids, vitamin A, vitamin D, vitamin C, folate, iron, and zinc. In the opinion of the authors, these nutrients were identified as representative of vitamins and minerals with sufficient research on their roles in the microbiome. The host responses to the gut microbiome will also be discussed. Future direction in microbiome research, for example, precision microbiome, will be proposed.

Keywords:  Intestinal immunity; Meta-omics; Microbiome homeostasis; Microbiome-host interaction; Precision microbiome

DOI:  https://doi.org/10.1016/j.nutres.2023.02.007
Nat Immunol. 2023 Mar 30.

Monocytes can proliferate in vacant niches before differentiation into macrophages.

DOI: https://doi.org/10.1038/s41590-023-01480-7
Semin Immunol. 2023 Mar 27. pii: S1044-5323(23)00046-5. [Epub ahead of print]67 101755

Microbial metabolites and immunotherapy: Basic rationale and clinical indications.

Larisa V Kovtonyuk, Kathy D McCoy.

  Our microbiota has a critical role in shaping host immunity. Microbes that reside in the gut harbor a large metabolic arsenal to aid in physiological functions of the host. Microbial metabolites, which are products of microbial metabolism, such as short chain fatty acids (SCFA), purine metabolites, cyclic dinucleotides, tryptophan derivatives, and secondary bile acids, can tailor the host immune cell landscape in homeostasis and during cancer immunotherapy. The critical role of the microbiome in aiding immune checkpoint blockade therapies has become clearer over the past few years, with the most recent studies providing more detailed mechanistic insight on how microbes and their metabolites control the outcome of immunotherapy. This review summarizes recent studies on how microbial metabolites orchestrate immune responses during cancer immunotherapies.

Keywords:  Cancer immunotherapy; Gut microbiome; Microbial metabolites

DOI:  https://doi.org/10.1016/j.smim.2023.101755
Front Immunol. 2023 ;14 1140749

Metabolic regulation of dendritic cell activation and immune function during inflammation.

Lili Wu, Ziqi Yan, Yiyang Jiang, Yingyi Chen, Juan Du, Lijia Guo, Junji Xu, Zhenhua Luo, Yi Liu.

  Dendritic cells (DCs) are antigen-presenting cells that bridge innate and adaptive immune responses. Multiple cell types, including DCs, rely on cellular metabolism to determine their fate. DCs substantially alter cellular metabolic pathways during activation, such as oxidative phosphorylation, glycolysis, fatty acid and amino acid metabolism, which have crucial implications for their functionality. In this review, we summarize and discuss recent progress in DC metabolic studies, focusing on how metabolic reprogramming influences DC activation and functionality and the potential metabolic differences among DC subsets. Improving the understanding of the relationship between DC biology and metabolic regulation may provide promising therapeutic targets for immune-mediated inflammatory diseases.

Keywords:  cellular metabolism; dendritic cells (DC); glycolysis; inflammation; metabolic reprogramming

DOI:  https://doi.org/10.3389/fimmu.2023.1140749
Cell Host Microbe. 2023 Mar 22. pii: S1931-3128(23)00110-5. [Epub ahead of print]

Arresting microbiome development limits immune system maturation and resistance to infection in mice.

Jean-Bernard Lubin, Jamal Green, Sarah Maddux, Lidiya Denu, Tereza Duranova, Matthew Lanza, Meghan Wynosky-Dolfi, Julia N Flores, Logan P Grimes, Igor E Brodsky, Paul J Planet, Michael A Silverman.

  Disruptions to the intestinal microbiome during weaning lead to negative effects on host immune function. However, the critical host-microbe interactions during weaning that are required for immune system development remain poorly understood. We find that restricting microbiome maturation during weaning stunts immune system development and increases susceptibility to enteric infection. We developed a gnotobiotic mouse model of the early-life microbiome Pediatric Community (PedsCom). These mice develop fewer peripheral regulatory T cells and less IgA, hallmarks of microbiota-driven immune system development. Furthermore, adult PedsCom mice retain high susceptibility to Salmonella infection, which is characteristic of young mice and children. Altogether, our work illustrates how the post-weaning transition in microbiome composition contributes to normal immune maturation and protection from infection. Accurate modeling of the pre-weaning microbiome provides a window into the microbial requirements for healthy development and suggests an opportunity to design microbial interventions at weaning to improve immune development in human infants.

Keywords:  IgA; Salmonella; early life; germ-free; gnotobiotic; immune system development; microbiome; regulatory T cell; weaning

DOI:  https://doi.org/10.1016/j.chom.2023.03.006
Clin Transl Oncol. 2023 Mar 30.

Lung microbiome: an emerging player in lung cancer pathogenesis and progression.

Alexandra Karvela, Orsalia-Zoi Veloudiou, Anastasia Karachaliou, Theoni Kloukina, Georgia Gomatou, Elias Kotteas.

  The microbiome of the lungs, although until recently neglected, is now emerging as a potential contributor to chronic lung diseases, including cancer. Preclinical evidence suggests that the microbial burden of the lungs shapes the host immunity mechanisms and affects local antitumor immune responses. Studies of cohorts of patients with lung cancer reveal that different microbiome profiles are detected in patients with lung cancer compared to controls. In addition, an association between differential lung microbiome composition and distinct responses to immunotherapy has been suggested, yet, with limited data. Scarce evidence exists on the role of the lung microbiome in the development of metastases in the lungs. Interestingly, the lung microbiome is not isolated and interacts with the gut microbiome through a dynamic axis. Future research on the involvement of the lung microbiome in lung cancer pathogenesis and potential therapeutic implications is greatly anticipated.

Keywords:  Immune checkpoint inhibitors; Immunotherapy; Lung cancer; Lung microbiome; NSCLC

DOI:  https://doi.org/10.1007/s12094-023-03139-z
Front Cell Dev Biol. 2023 ;11 1147434

The diverse roles of macrophages in metabolic inflammation and its resolution.

Aleepta Guha Ray, Oluwatomilayo Patience Odum, Destini Wiseman, Ada Weinstock.

  Macrophages are one of the most functionally diverse immune cells, indispensable to maintain tissue integrity and metabolic health. Macrophages perform a myriad of functions ranging from promoting inflammation, through inflammation resolution to restoring and maintaining tissue homeostasis. Metabolic diseases encompass a growing list of diseases which develop from a mix of genetics and environmental cues leading to metabolic dysregulation and subsequent inflammation. In this review, we summarize the contributions of macrophages to four metabolic conditions-insulin resistance and adipose tissue inflammation, atherosclerosis, non-alcoholic fatty liver disease and neurodegeneration. The role of macrophages is complex, yet they hold great promise as potential therapies to address these growing health concerns.

Keywords:  atherosclerosis; diabetes; inflammation; macrophage; neuroinflammation; non-alcoholic fatty liver disease; obesity

DOI:  https://doi.org/10.3389/fcell.2023.1147434