bims-bac4me Biomed News
on Microbiome and trained immunity
Issue of 2023–04–23
eleven papers selected by
Chun-Chi Chang, Universitäts Spital Zürich
  1. Shaping of the alveolar landscape by respiratory infections and long-term consequences for lung immunity.
  2. Staphylococcus aureus induces tolerance in human monocytes accompanied with expression changes of cell surface markers.
  3. Modulation of innate immune memory dynamics by subcellular ROS.
  4. Intracellular persister: A stealth agent recalcitrant to antibiotics.
  5. Epigenomic regulation of macrophage polarization: Where do the nuclear receptors belong?
  6. Metabolic independence drives gut microbial colonization and resilience in health and disease.
  7. Novel fibroblast phenotypes in homeostasis and chronic inflammation: From functions to potential regulators.
  8. Good and bad outcomes of respiratory viral infections-influenza A virus trains sustained antitumor immunity of macrophages in the lung.
  9. Impact of the Microbiota on Viral Infections.
  10. Crosstalk between skin microbiota and immune system in health and disease.
  11. Gut microbiota and its metabolites: Bridge of dietary nutrients and Alzheimer's disease.
  1. Front Immunol. 2023 ;14 1149015
    Shaping of the alveolar landscape by respiratory infections and long-term consequences for lung immunity.
    Lucia Rodriguez-Rodriguez, Laurent Gillet, Bénédicte Machiels.
      Respiratory infections and especially viral infections, along with other extrinsic environmental factors, have been shown to profoundly affect macrophage populations in the lung. In particular, alveolar macrophages (AMs) are important sentinels during respiratory infections and their disappearance opens a niche for recruited monocytes (MOs) to differentiate into resident macrophages. Although this topic is still the focus of intense debate, the phenotype and function of AMs that recolonize the niche after an inflammatory insult, such as an infection, appear to be dictated in part by their origin, but also by local and/or systemic changes that may be imprinted at the epigenetic level. Phenotypic alterations following respiratory infections have the potential to shape lung immunity for the long-term, leading to beneficial responses such as protection against allergic airway inflammation or against other infections, but also to detrimental responses when associated with the development of immunopathologies. This review reports the persistence of virus-induced functional alterations in lung macrophages, and discusses the importance of this imprinting in explaining inter-individual and lifetime immune variation.
    Keywords:  AM ontogeny; alveolar macrophages; lung immunity; niche imprinting; respiratory viruses; trained immunity
    DOI:  https://doi.org/10.3389/fimmu.2023.1149015
  2. Front Immunol. 2023 ;14 1046374
    Staphylococcus aureus induces tolerance in human monocytes accompanied with expression changes of cell surface markers.
    Mario M Müller, Christian Baldauf, Stella Hornischer, Tilman E Klassert, Antony Schneegans, Andrea Behnert, Mathias W Pletz, Stefan Hagel, Hortense Slevogt.
      Exposure of human monocytes to lipopolysaccharide (LPS) or other pathogen-associated molecular pattern (PAMPs) induces a temporary insensitivity to subsequent LPS challenges, a cellular state called endotoxin tolerance (ET), associated with the pathogenesis of sepsis. In this study, we aimed to characterize the cellular state of human monocytes from healthy donors stimulated with Staphylococcus aureus in comparison to TLR2-specific ligands. We analyzed S. aureus induced gene expression changes after 2 and 24 hours by amplicon sequencing (RNA-AmpliSeq) and compared the pro-inflammatory response after 2 hours with the response in re-stimulation experiments. In parallel, glycoprotein expression changes in human monocytes after 24 hours of S. aureus stimulation were analyzed by proteomics and compared to stimulation experiments with TLR2 ligands Malp-2 and Pam3Cys and TLR4 ligand LPS. Finally, we analyzed peripheral blood monocytes of patients with S. aureus bloodstream infection for their ex vivo inflammatory responses towards S. aureus stimulation and their glycoprotein expression profiles. Our results demonstrate that monocytes from healthy donors stimulated with S. aureus and TLR ligands of Gram-positive bacteria entered the tolerant cell state after activation similar to LPS treatment. In particular reduced gene expression of pro-inflammatory cytokines (TNF, IL1β) and chemokines (CCL20, CCL3, CCL4, CXCL2, CXCL3 and CXCL8) could be demonstrated. Glycoprotein expression changes in monocytes tolerized by the different TLR agonists were highly similar while S. aureus-stimulated monocytes shared some of the PAMP-induced changes but also exhibited a distinct expression profile. 11 glycoproteins (CD44, CD274, DSC2, ICAM1, LAMP3, LILRB1, PTGS2, SLC1A3, CR1, FGL2, and HP) were similarly up- or downregulated in all four comparisons in the tolerant cell state. Monocytes from patients with S. aureus bacteremia revealed preserved pro-inflammatory responsiveness to S. aureus stimulation ex vivo, expressed increased CD44 mRNA but no other glycoprotein of the tolerance signature was differentially expressed.
    Keywords:  S. aureus; bacteremia; glycoproteins; marker of tolerance; membrane proteins; monocyte; proteomics; tolerance
    DOI:  https://doi.org/10.3389/fimmu.2023.1046374
  3. Antioxid Redox Signal. 2023 Apr 21.
    Modulation of innate immune memory dynamics by subcellular ROS.
    Shuo Geng, RuiCi Lin, Yajun Wu, Jing Wang, Liwu Li.
       SIGNIFICANCE: Innate immune cells adopt distinct memory states during the pathogenesis of acute and chronic inflammatory diseases. Intracellular generations of reactive oxygen species (ROS) play key roles during the programming dynamics of innate immune cells such as monocytes and macrophages.
    RECENT ADVANCES: ROS modulates the adaptation of innate leukocytes to varying intensities and durations of inflammatory signals, facilitates fundamental reprogramming dynamics such as priming, tolerance and exhaustion, in addition to fundamental processes of proliferation, differentiation, phagocytosis, chemotaxis, as well as expression of pro- and anti-inflammatory mediators. ROS can be generated at distinct subcellular compartments including cellular membrane, mitochondria, and peroxisome. Complex inflammatory signals may finely regulate ROS generation within distinct subcellular compartments which in turn may differentially facilitate innate memory dynamics.
    CRITICAL ISSUES: Complex inflammatory signals with varying strength and durations may differentially trigger ROS generation at peroxisome, mitochondria and other subcellular organelles. Peroxisomal or mitochondrial ROS may facilitate the assembly of distinct signaling platforms involved in the programming of memory innate leukocytes. Despite the emerging connection of subcellular ROS with innate immune memory, underlying mechanisms are still not well defined.
    FUTURE DIRECTIONS: Recent important discoveries linking subcellular ROS and innate memory as critically reviewed here hold novel translational relevance related to acute and chronic inflammatory diseases. Capitalizing on these novel findings, future systems studies that employ next-gen single cell dynamics analyses in response to complex inflammatory environments are urgently needed in order to comprehensively decipher the programming dynamics of innate immune memory, finely modulated by subcellular ROS.
    DOI:  https://doi.org/10.1089/ars.2023.0304
  4. Front Cell Infect Microbiol. 2023 ;13 1141868
    Intracellular persister: A stealth agent recalcitrant to antibiotics.
    Nicolas Personnic, Patricia Doublet, Sophie Jarraud.
      The bulk of bacteria transiently evading appropriate antibiotic regimes and recovered from non-resolutive infections are commonly refer to as persisters. In this mini-review, we discuss how antibiotic persisters stem from the interplay between the pathogen and the cellular defenses mechanisms and its underlying heterogeneity.
    Keywords:  antibiotic; heterogeneity; infection; persisters; virulence
    DOI:  https://doi.org/10.3389/fcimb.2023.1141868
  5. Immunol Rev. 2023 Apr 19.
    Epigenomic regulation of macrophage polarization: Where do the nuclear receptors belong?
    Zsolt Czimmerer, Laszlo Nagy.
      Our laboratory has a long-standing research interest in understanding how lipid-activated transcription factors, nuclear hormone receptors, contribute to dendritic cell and macrophage gene expression regulation, subtype specification, and responses to a changing extra and intracellular milieu. This journey in the last more than two decades took us from identifying target genes for various RXR heterodimers to systematically mapping nuclear receptor-mediated pathways in dendritic cells to identifying hierarchies of transcription factors in alternative polarization in macrophages to broaden the role of nuclear receptors beyond strictly ligand-regulated gene expression. We detail here the milestones of the road traveled and draw conclusions regarding the unexpectedly broad role of nuclear hormone receptors as epigenomic components of dendritic cell and macrophage gene regulation as we are getting ready for the next challenges.
    Keywords:  EGR2; IL-4; PPARγ; STAT6; epigenome; macrophage; nuclear receptors; polarization; transcriptional regulation
    DOI:  https://doi.org/10.1111/imr.13209
  6. Genome Biol. 2023 Apr 17. 24(1): 78
    Metabolic independence drives gut microbial colonization and resilience in health and disease.
    Andrea R Watson, Jessika Füssel, Iva Veseli, Johanna Zaal DeLongchamp, Marisela Silva, Florian Trigodet, Karen Lolans, Alon Shaiber, Emily Fogarty, Joseph M Runde, Christopher Quince, Michael K Yu, Arda Söylev, Hilary G Morrison, Sonny T M Lee, Dina Kao, David T Rubin, Bana Jabri, Thomas Louie, A Murat Eren.
       BACKGROUND: Changes in microbial community composition as a function of human health and disease states have sparked remarkable interest in the human gut microbiome. However, establishing reproducible insights into the determinants of microbial succession in disease has been a formidable challenge.
    RESULTS: Here we use fecal microbiota transplantation (FMT) as an in natura experimental model to investigate the association between metabolic independence and resilience in stressed gut environments. Our genome-resolved metagenomics survey suggests that FMT serves as an environmental filter that favors populations with higher metabolic independence, the genomes of which encode complete metabolic modules to synthesize critical metabolites, including amino acids, nucleotides, and vitamins. Interestingly, we observe higher completion of the same biosynthetic pathways in microbes enriched in IBD patients.
    CONCLUSIONS: These observations suggest a general mechanism that underlies changes in diversity in perturbed gut environments and reveal taxon-independent markers of "dysbiosis" that may explain why widespread yet typically low-abundance members of healthy gut microbiomes can dominate under inflammatory conditions without any causal association with disease.
    Keywords:  Fecal microbiota transplantation; Human gut microbiome; Metabolic independence; Microbial colonization; Microbial metabolism
    DOI:  https://doi.org/10.1186/s13059-023-02924-x
  7. J Physiol. 2023 Apr 16.
    Novel fibroblast phenotypes in homeostasis and chronic inflammation: From functions to potential regulators.
    Haruka Miki, Mario C Manresa.
      Fibroblasts are essential components of the stroma that gives sustain to a variety of tissues and are key to the process of tissue repair after injury. Their role in tissue repair has been attributed to their ability to acquire a contractile, extracellular matrix (ECM)-producing phenotype known as myofibroblast. This property is primarily dependent on their response to the pleiotropic cytokine transforming growth factor (TGF)-β1. Until recently, the potential role of fibroblasts in other homeostatic and disease-related processes was less well understood. Although in vitro studies indicated that fibroblasts are able to respond to and secrete inflammatory mediators, definitive evidence of their contribution to chronic inflammation was limited. However, the emergence of techniques that allow exploring tissues at the single cell level has challenged the previous paradigms on fibroblast identity and functions and led to the discovery of significant diversity, showing the presence of fibroblasts with alternate transcriptional profiles in a variety of tissues. These studies have also suggested potential roles of novel fibroblast subtypes as regulators of epithelial homeostasis and renewal, inflammatory cell infiltration and activation, as well as antigen presentation. In this manuscript we make a comprehensive review of recent literature on fibroblast diversity in the digestive tract, skin, lungs and joints. We review evidence of their contribution to the regulation of homeostasis and chronic inflammation as well as their interactions with other cells in various tissue compartments. We also discuss evidence of different factors involved in the control of fibroblast function, addressing the role of various cytokines, transcription factors and epigenetic changes, as well as microenvironmental factors including ECM stiffness, hypoxia and metabolic shifts. Abstract figure legend Our abstract presents a summary of the concepts explored in this review, including the role of fibroblasts on epithelial maintenance during homeostasis, the response of these cells to inflammatory mediators from their environment, their ability to recruit immune cells and to differentiate into fibrogenic myofibroblasts. This article is protected by copyright. All rights reserved.
    Keywords:  Fibroblasts; chronic inflammation; diversity; fibrosis and cell-cell interactions; homeostasis
    DOI:  https://doi.org/10.1113/JP284620
  8. Cell Mol Immunol. 2023 Apr 17.
    Good and bad outcomes of respiratory viral infections-influenza A virus trains sustained antitumor immunity of macrophages in the lung.
    Sabine Stegemann-Koniszewski, Sarah Frentzel, Dunja Bruder.
      
    DOI:  https://doi.org/10.1038/s41423-023-01015-y
  9. Annu Rev Virol. 2023 Apr 18.
    Impact of the Microbiota on Viral Infections.
    Danielle E Campbell, Yuhao Li, Harshad Ingle, Megan T Baldridge.
      The mammalian gastrointestinal tract (GIT) hosts a diverse and highly active microbiota composed of bacteria, eukaryotes, archaea, and viruses. Studies of the GIT microbiota date back more than a century, although modern techniques, including mouse models, sequencing technology, and novel therapeutics in humans, have been foundational to our understanding of the roles of commensal microbes in health and disease. Here, we review the impacts of the GIT microbiota on viral infection, both within the GIT and systemically. GIT-associated microbes and their metabolites alter the course of viral infection through a variety of mechanisms, including direct interactions with virions, alteration of the GIT landscape, and extensive regulation of innate and adaptive immunity. Mechanistic understanding of the full breadth of interactions between the GIT microbiota and the host is still lacking in many ways but will be vital for the development of novel therapeutics for viral and nonviral diseases alike. Expected final online publication date for the Annual Review of Virology, Volume 10 is September 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
    DOI:  https://doi.org/10.1146/annurev-virology-111821-115754
  10. Nat Immunol. 2023 Apr 20.
    Crosstalk between skin microbiota and immune system in health and disease.
    Qian Liu, Ryan Ranallo, Carmen Rios, Elizabeth A Grice, Kyung Moon, Richard L Gallo.
      
    DOI:  https://doi.org/10.1038/s41590-023-01500-6
  11. Adv Nutr. 2023 Apr 17. pii: S2161-8313(23)00290-9. [Epub ahead of print]
    Gut microbiota and its metabolites: Bridge of dietary nutrients and Alzheimer's disease.
    Guangsu Zhu, Jianxin Zhao, Hao Zhang, Gang Wang, Wei Chen.
      Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment and neuroinflammation. Recent research has revealed the crucial role of the gut microbiota and microbial metabolites in modulating AD. However, mechanisms by which the microbiome and microbial metabolites affect brain function remain poorly understood. Here, we review the literature on changes in the diversity and composition of the gut microbiome in AD patients and in animal models of AD. We also discuss the latest progress in understanding the pathways by which the gut microbiota and microbial metabolites from the host or diet regulate AD. By understanding the effects of dietary components on brain function, the microbiota composition and microbial metabolites, we examine the potential for manipulation of the gut microbiota through dietary intervention to delay the progress of AD. Although it is challenging to translate our understanding of microbiome-based approaches to dietary guidelines or clinical therapies, these findings provide an attractive target for promoting brain function.
    Keywords:  Alzheimer’s disease; Dietary interventions; Gut microbiota; Microbial metabolites; Microbiota-gut-brain axis
    DOI:  https://doi.org/10.1016/j.advnut.2023.04.005
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