Systemic instruction of cell-mediated immunity by the intestinal microbiome - PubMed (original) (raw)

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Systemic instruction of cell-mediated immunity by the intestinal microbiome

John Grainger et al. F1000Res. 2018.

Abstract

Recent research has shed light on the plethora of mechanisms by which the gastrointestinal commensal microbiome can influence the local immune response in the gut (in particular, the impact of the immune system on epithelial barrier homeostasis and ensuring microbial diversity). However, an area that is much less well explored but of tremendous therapeutic interest is the impact the gut microbiome has on systemic cell-mediated immune responses. In this commentary, we highlight some key studies that are beginning to broadly examine the different mechanisms by which the gastrointestinal microbiome can impact the systemic immune compartment. Specifically, we discuss the effects of the gut microbiome on lymphocyte polarisation and trafficking, tailoring of resident immune cells in the liver, and output of circulating immune cells from the bone marrow. Finally, we explore contexts in which this new understanding of long-range effects of the gut microbiome can have implications, including cancer therapies and vaccination.

Keywords: commensal; gut bacteria; immune; microbiome.

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Conflict of interest statement

No competing interests were disclosed.No competing interests were disclosed.No competing interests were disclosed.

Figures

Figure 1.

Figure 1.. Effects of gut microbiota on systemic cell-mediated immune responses in health and disease.

Much of the mucosal immune response towards the gut microbiota is focused on maintaining microbial diversity and supporting epithelial barrier function. Mechanisms include local production of immunoglobulin A (IgA) and production of the cytokine interleukin-22 (IL-22) to re-enforce epithelial barrier integrity. Even in the intact barrier, however, microbiota-derived ligands and metabolites enter into the circulatory system and impact immune populations at distal sites. These effects include tailoring of immune cell function in the liver and modulating bone marrow haematopoiesis. In disease states, the gastrointestinal barrier can become more leaky, leading to aberrant exposure to factors from the microbiome, as occurs in alcoholic liver disease. Additionally, in mouse models of T helper type 17 (Th17)-associated pathology (K/BxN arthritis and experimental autoimmune encephalomyelitis [EAE]), Th17 cells generated in response to commensal bacteria are thought to traffic from the gut and impact antibody generation and inflammation systemically. CNS, central nervous system; DC, dendritic cell; ILC, innate lymphoid cell; iNKT cell, invariant natural killer T cell; LSEC, liver sinusoidal endothelial cell; SCFA, short-chain fatty acid; TLR, Toll-like receptor.

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