Gut Microbial Antigenic Mimicry in Autoimmunity

Garabatos, Nahir; Santamaría, Pere

doi:10.3389/fimmu.2022.873607

Cited by 41 publications

(34 citation statements)

References 181 publications

(181 reference statements)

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“…The disruption of the epithelial barrier function occurs in the preclinical phase of RA in murine models and humans (Tajik et al, 2020;Audo et al, 2022). Gut dysbiosis might trigger the breakdown of gut barrier integrity and the leakage of microbiota or their metabolites into gut tissue and even venous or lymphatic circulation, enabling exposure of the immune cells to bacterial antigens leading to local and systemic inflammation, increased pro-inflammatory cytokines such as TNF-a and IL-17A, and differentiation of autoreactive Th17 cells (Figure 2) (Berthelot et al, 2019;Chiang et al, 2019;Man et al, 2020;Tajik et al, 2020;Garabatos and Santamaria, 2022;Zhao et al, 2022). The migration of self-reactive cells to the joints can cause cartilage and bone damage (Zhao et al, 2022).…”

Section: Alterations In Gut Barrier Functionmentioning

confidence: 99%

“…Lactobacillus and Bifidobacterium could limit the development of autoimmune diseases in genetically susceptible individuals by increasing the expression of TJ proteins (Hills et al, 2019). Bacteroides fragilis sphingolipids promote gut barrier integrity (Garabatos and Santamaria, 2022).…”

Section: Alterations In Gut Barrier Functionmentioning

confidence: 99%

“…The molecular mimicry or crossreactivity hypothesis proposes that an exogenous substance (i.e., a microbial agent with antigenic similarity to self-antigens) may trigger an immune response against self-antigens (Rashid and Ebringer, 2012). Prevotella contributes to arthritis development in mice by activating autoreactive T cells specific for the arthritisrelevant autoantigen Ribosomal Protein L23a (RPL23A) (Garabatos and Santamaria, 2022). Similarly, peptides derived from Bacteroides fragilis, Candida albicans, and Streptococcus sanguis are similar to collagen-type-II and induced cross-reactive responses in the CIA model (Costalonga et al, 2002;Yordanov et al, 2005;Zheng et al, 2020;Zhou et al, 2020).…”

Section: Molecular Mimicrymentioning

confidence: 99%

“…Gut dysbiosis can lead to inflammation in the intestinal mucosa and tissue damage, promoting the loss of immune tolerance and the development of autoimmunity (Inda et al, 2019). Gut microbiota, primarily through microbiota-derived metabolites, has a role in regulating T cell functions and could disrupt gut immune homeostasis through abnormal antigen presentation and modulating the adaptive immunity, especially in the polarization of näive T cells to Th17 cells and generation of autoreactive B cells (Lin and Zhang, 2017;Wang et al, 2019b;Di Gangi et al, 2020;Zhang et al, 2020;Garabatos and Santamaria, 2022;Marazzato et al, 2022). Gut dysbiosis leads to inflammation by alterations in the ratio of Th17/Treg cells and an imbalance of Tfh/Tfr cells.…”

Section: Gut Dysbiosis Induces the Development Of Chronic Inflammatio...mentioning

confidence: 99%

“…In the mouse gut, colonic Treg induced by Clostridium bacteria are vital players in gut homeostasis and prevent colitis (Alameddine et al, 2019). In the human colon microbiota, Clostridium IV Faecalibacterium prausnitzii induces the formation of Treg cells via the activation of dendritic cells and causes the secretion of IL-10 by T cells (Garabatos and Santamaria, 2022;Wang et al, 2022b). Another gut bacteria, Bacteroides fragilis, via its carbohydrate antigen polysaccharide A (PSA), may promote the differentiation of Treg in vitro or mice through dendritic cell modulation.…”

Section: Gut Microbiota Can Modulate the Th17/treg Balancementioning

confidence: 99%

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Gut-joint axis: Gut dysbiosis can contribute to the onset of rheumatoid arthritis via multiple pathways

Romero-Figueroa

Ramírez-Durán²,

Montiel-Jarquín³

et al. 2023

Front. Cell. Infect. Microbiol.

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Rheumatoid Arthritis (RA) is an autoimmune disease characterized by loss of immune tolerance and chronic inflammation. It is pathogenesis complex and includes interaction between genetic and environmental factors. Current evidence supports the hypothesis that gut dysbiosis may play the role of environmental triggers of arthritis in animals and humans. Progress in the understanding of the gut microbiome and RA. has been remarkable in the last decade. In vitro and in vivo experiments revealed that gut dysbiosis could shape the immune system and cause persistent immune inflammatory responses. Furthermore, gut dysbiosis could induce alterations in intestinal permeability, which have been found to predate arthritis onset. In contrast, metabolites derived from the intestinal microbiota have an immunomodulatory and anti-inflammatory effect. However, the precise underlying mechanisms by which gut dysbiosis induces the development of arthritis remain elusive. This review aimed to highlight the mechanisms by which gut dysbiosis could contribute to the pathogenesis of RA. The overall data showed that gut dysbiosis could contribute to RA pathogenesis by multiple pathways, including alterations in gut barrier function, molecular mimicry, gut dysbiosis influences the activation and the differentiation of innate and acquired immune cells, cross-talk between gut microbiota-derived metabolites and immune cells, and alterations in the microenvironment. The relative weight of each of these mechanisms in RA pathogenesis remains uncertain. Recent studies showed a substantial role for gut microbiota-derived metabolites pathway, especially butyrate, in the RA pathogenesis.

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Section: Alterations In Gut Barrier Functionmentioning

confidence: 99%

Section: Alterations In Gut Barrier Functionmentioning

confidence: 99%

Section: Molecular Mimicrymentioning

confidence: 99%

Section: Gut Dysbiosis Induces the Development Of Chronic Inflammatio...mentioning

confidence: 99%

Section: Gut Microbiota Can Modulate the Th17/treg Balancementioning

confidence: 99%

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Gut-joint axis: Gut dysbiosis can contribute to the onset of rheumatoid arthritis via multiple pathways

Romero-Figueroa

Ramírez-Durán²,

Montiel-Jarquín³

et al. 2023

Front. Cell. Infect. Microbiol.

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Epstein–Barr virus infection, B‐cell dysfunction and other risk factors converge in gut‐associated lymphoid tissue to drive the immunopathogenesis of multiple sclerosis: a hypothesis

et al. 2022

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Multiple sclerosis is associated with Epstein–Barr virus (EBV) infection, B‐cell dysfunction, gut dysbiosis, and environmental and genetic risk factors, including female sex. A disease model incorporating all these factors remains elusive. Here, we hypothesise that EBV‐infected memory B cells (MBCs) migrate to gut‐associated lymphoid tissue (GALT) through EBV‐induced expression of LPAM‐1, where they are subsequently activated by gut microbes and/or their products resulting in EBV reactivation and compartmentalised anti‐EBV immune responses. These responses involve marginal zone (MZ) B cells that activate CD4 + T‐cell responses, via HLA‐DRB1, which promote downstream B‐cell differentiation towards CD11c + /T‐bet + MBCs, as well as conventional MBCs. Intrinsic expression of low‐affinity B‐cell receptors (BCRs) by MZ B cells and CD11c + /T‐bet + MBCs promotes polyreactive BCR/antibody responses against EBV proteins (e.g. EBNA‐1) that cross‐react with central nervous system (CNS) autoantigens (e.g. GlialCAM). EBV protein/autoantigen‐specific CD11c + /T‐bet + MBCs migrate to the meningeal immune system and CNS, facilitated by their expression of CXCR3, and induce cytotoxic CD8 + T‐cell responses against CNS autoantigens amplified by BAFF, released from EBV‐infected MBCs. An increased abundance of circulating IgA + MBCs, observed in MS patients, might also reflect GALT‐derived immune responses, including disease‐enhancing IgA antibody responses against EBV and gut microbiota‐specific regulatory IgA + plasma cells. Female sex increases MZ B‐cell and CD11c + /T‐bet + MBC activity while environmental risk factors affect gut dysbiosis. Thus, EBV infection, B‐cell dysfunction and other risk factors converge in GALT to generate aberrant B‐cell responses that drive pathogenic T‐cell responses in the CNS.

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Immunologic derangement caused by intestinal dysbiosis and stress is the intrinsic basis of reactive arthritis

He,

Qian

2024

Z Rheumatol

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Reactive arthritis (ReA) is defined as arthritis resulting from infections in other body parts, such as the gastrointestinal and urogenital tracts. The primary clinical manifestations involve acute-onset and self-limiting asymmetric large joint inflammation in the lower limbs. Although bacterial or chlamydia infections have long been recognized as playing a pivotal role in its pathogenesis, recent studies suggest that antibiotic treatment may perpetuate rather than eradicate chlamydia within the host, indicating an involvement of other mechanisms in Reactive arthritis. Reactive arthritis is currently believed to be associated with infection, genetic marker (HLA-B27), and immunologic derangement. As an autoimmune disease, increasing attention has been given to understanding the role of the immune system in Reactive arthritis. This review focuses on elucidating how the immune system mediates reactive arthritis and explores the roles of intestinal dysbiosis-induced immune disorders and stress-related factors in autoimmune diseases, providing novel insights into understanding reactive arthritis.

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Gut Microbial Antigenic Mimicry in Autoimmunity

Cited by 41 publications

References 181 publications

Gut-joint axis: Gut dysbiosis can contribute to the onset of rheumatoid arthritis via multiple pathways

Gut-joint axis: Gut dysbiosis can contribute to the onset of rheumatoid arthritis via multiple pathways

Epstein–Barr virus infection, B‐cell dysfunction and other risk factors converge in gut‐associated lymphoid tissue to drive the immunopathogenesis of multiple sclerosis: a hypothesis

Immunologic derangement caused by intestinal dysbiosis and stress is the intrinsic basis of reactive arthritis

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