Interactions Between the Gut Microbiota and the Host Innate Immune Response Against Pathogens

Abstract

The mammalian intestine is colonized by over a trillion microbes that comprise the "gut microbiota," a microbial community which has co-evolved with the host to form a mutually beneficial relationship. Accumulating evidence indicates that the gut microbiota participates in immune system maturation and also plays a central role in host defense against pathogens. Here we review some of the mechanisms employed by the gut microbiota to boost the innate immune response against pathogens present on epithelial mucosal surfaces. Antimicrobial peptide secretion, inflammasome activation and induction of host IL-22, IL-17, and IL-10 production are the most commonly observed strategies employed by the gut microbiota for host anti-pathogen defense. Taken together, the body of evidence suggests that the host gut microbiota can elicit innate immunity against pathogens.

Keywords: IL-10; IL-17; IL-22; antimicrobial peptides; gut microbiota; host innate immunity; inflammasome.

Figure 1

Gut microbiota plays an important role in the induction of antimicrobial peptides expression against pathogens. Antimicrobial peptides are key components of innate immunity to control pathogen growth within the intestine. Accumulated evidence identified that gut microbiota can contribute to the expression of antimicrobial peptides and play a central role in host defense against pathogens. Paneth cells could directly sense gut microbiota through cell-autonomous myeloid differentiation primary response 88 (MyD88)-dependent toll-like receptor (TLR) activation, triggering expression of α-defensins and C-type lectins. With regard to β-defensin, gut microbiota induce β-defensin expression in cell culture mediated by NF-κB- and MAPK/AP-1-dependent pathways in vitro. Then β-defensin interacts with intestinal epithelial cell (IEC) through CCR6 to activate epithelial restitution and barrier repair.

Figure 2

Gut microbiota enhance the expression of IL-22 against invading pathogens. IL-22 is important in maintaining the integrity of mucosal barriers and can be produced by many different types innate immune cells, which induce the expression of various antimicrobial proteins, including lipocalin-2, calprotectin, C-type lectins, S100A8, S100A9, and so on to clear pathogens. Increasing evidence identified that gut microbiota enhances the expression of IL-22 to protect the host against pathogens. The results show that gut microbiota utilize tryptophan as an energy source and produce a metabolite, indole-3-aldehyde (IAld), which in turns activated Ahr on innate immune cells. Once activated, innate immune cells will secrete IL-22, which protects the host against opportunistic pathogens by reducing their colonization.