The functional impact of the intestinal microbiome on mucosal immunity and systemic autoimmunity - PubMed (original) (raw)

Review

The functional impact of the intestinal microbiome on mucosal immunity and systemic autoimmunity

Randy S Longman et al. Curr Opin Rheumatol. 2015 Jul.

Abstract

Purpose of review: This review will highlight recent advances functionally linking the gut microbiome with mucosal and systemic immune cell activation underlying autoimmunity.

Recent findings: Dynamic interactions between the gut microbiome and environmental cues (including diet and medicines) shape the effector potential of the microbial organ. Key bacteria and viruses have emerged that, in defined microenvironments, play a critical role in regulating effector lymphocyte functions. The coordinated interactions between these different microbial kingdoms - including bacteria, helminths, and viruses (termed transkingdom interactions) - play a key role in shaping immunity. Emerging strategies to identify immunologically relevant microbes with the potential to regulate immune cell functions both at mucosal sites and systemically will likely define diagnostic and therapeutic targets.

Summary: The microbiome constitutes a critical microbial organ with coordinated interactions that shape host immunity.

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Figures

Figure 1

Figure 1. Microbial Regulation of Immunity and Autoimmunity

Homeostatic induction is maintained by sentinel microbes in which the barrier remains intact. Representative adherent microbes such as the mouse commensal segmented filamentous bacteria (SFB) tethers to the ileal mucosa and induces antigen-specific Th17 polarization. Similarly, key clostridial species promote the differentiation of induced Treg cells. Viruses, such as mouse norovirus (MNV), are sufficient to promote lymphocyte homeostasis in the lamina propria via an IFNα-dependent mechanism. Homeostatic inhibition is achieved by re-enforcing intestinal compartmentalization of microbes. Microbial activation of CX3CR1+ mononuclear phagocytes regulates group 3 innate lymphoid cells (ILC3) to produce the key cytokine IL-22 which promotes mucosal healing, anti-microbial peptide production, and modification of carbohydrates for bacteria. Homeostatic breakdown variably alters these mechanisms, resulting in trafficking of luminal microbes to mesenteric lymph nodes by CX3CR1+ MNPs, aberrant immunity to commensal microbiota, and subsequent systemic autoimmunity.

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References

    1. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA. Diversity of the human intestinal microbial flora. Science. 2005;308(5728):1635–1638. - PMC - PubMed
    1. Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: Human gut microbes associated with obesity. Nature. 2006;444(7122):1022–1023. - PubMed
    1. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59–65. - PMC - PubMed
    1. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP, Egholm M, et al. A core gut microbiome in obese and lean twins. Nature. 2009;457(7228):480–484. - PMC - PubMed
    1. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027–1031. - PubMed

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