Microbiota and host immune responses: a love-hate relationship

Abstract

A complex relationship between the microbiota and the host emerges early at birth and continues throughout life. The microbiota includes the prokaryotes, viruses and eukaryotes living among us, all of which interact to different extents with various organs and tissues in the body, including the immune system. Although the microbiota is most dense in the lower intestine, its influence on host immunity extends beyond the gastrointestinal tract. These interactions with the immune system operate through the actions of various microbial structures and metabolites, with outcomes ranging from beneficial to deleterious for the host. These differential outcomes are dictated by host factors, environment, and the type of microbes or products present in a specific ecosystem. It is also becoming clear that the microbes are in turn affected and respond to the host immune system. Disruption of this complex dialogue between host and microbiota can lead to immune pathologies such as inflammatory bowel diseases, diabetes and obesity. This review will discuss recent advances regarding the ways in which the host immune system and microbiota interact and communicate with one another.

Keywords: host-microbe interactions; immunology; microbiota.

© 2015 John Wiley & Sons Ltd.

Figures

Figure 1

The microbiota affects local and systemic immunity. The intestine (1) contains the greatest number and diversity of microbiota members. Proteobacteria, specifically Sutterella, alter faecal IgA levels, likely through degradation of SIgA. SFB also alter IgA levels by promoting the expansion of germinal centres and inducing IgA‐secreting cells in Peyer's patches, isolated lymphoid follicles, and tertiary lymphoid tissue. MHCII‐dependent SFB antigen presentation on intestinal DCs induces Th17 cell differentiation, while MHCII‐dependent SFB antigen presentation by ILCs constrains Th17 cell differentiation. The intestinal microbiota also influences systemic immunity, including the number and function of circulating neutrophils (2) as well as constraining iNKT levels in the lung (3) and colon (1). DC, dendritic cell; ILCs, innate lymphoid cells; iNKT, invariant natural killer T cell; SFB, segmented filamentous bacteria; SIgA, secretory immunoglobulin A; Th17, T helper 17 lymphocyte; Treg, T regulatory lymphocyte.

Figure 2

Bacterial components that affect innate and adaptive immunity in the intestine. Bacterial MAMPS signal through host PRRs. PSA (A) fromBacteroides fragilis interacts with TLR2 on plasmacytoid pDCs to induce IL‐10 production from CD4+ T cells and Treg clonal expansion. Lactobacillus plantarum d‐alanylated teichoic acid (D) also signals through TLR2 on DCs to modulate effector and regulatory T‐cell populations. Flagellin activation of TLR5 on epithelial cells alters microbiota composition. Luminal bacteria promote mucus secretion and movement of monocytes closer to epithelial stem cells through a MyD88‐dependent signalling pathway. Sphingolipid metabolites from B. fragilis promote iNKT activation in adults. SCFA metabolites from bacteria impact immunity through multiple mechanisms: activation of GPRs, inhibition of HDACs, and regulation of autophagy. Butyrate exerts anti‐inflammatory effects on macrophages through HDAC inhibition and promotes barrier function in IECs through stabilization of HIF. Lactobacilli produce an AhR ligand, indole‐3‐aldehyde, which induces IL‐22, promoting AMP expression and mucosal homeostasis. AhR signalling on ILC3s also inhibits Th17 cell expansion. AhR, aryl hydrocarbon receptor; AMPs, antimicrobial peptides; GPRs, G protein‐coupled receptors; HIF, hypoxia‐inducible factor; I, indole‐3‐aldehyde, an AhR ligand; IECs, intestinal epithelial cells, ILC3, group 3 innate lymphoid cell; MAMPS, microbe‐associated molecular patterns; MyD88, myeloid differentiation primary response protein 88; PRRs, pattern recognition receptors; pDCs, plasmacytoid dendritic cells; PSA, polysaccharide A fromBacteroides fragilis; SCFAs, short‐chain fatty acids; TLRs, Toll‐like receptors.