Microbiota-stimulated immune mechanisms to maintain gut homeostasis

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In recent years there has been an explosion of interest to identify microbial inhabitants of human and understand their beneficial role in health. In the gut, a symbiotic host–microbial interaction has coevolved as bacteria make essential contributions to human metabolism and bacteria in turn benefits from the nutrient-rich niche in the intestine. To maintain host–microbe coexistence, the host must protect itself against microbial invasion, injury, and overreactions to foreign food antigens, and gut microbes need protection against competing microbes and the host immune system. Perturbation of this homeostatic coexistence has been strongly associated with human disease. This review discusses how gut bacteria regulate host innate and adaptive immunity, with emphasis on how this regulation contributes to host–microbe homeostasis in the gut.

Section snippets

Developmental defects in germ-free animals

Microbes are essential for mammalian health. The long list of developmental defects in germ-free (GF, sterile) mice includes decreased metabolic rate, defects in vasculature, and altered intestinal morphology and motility [24]. The immune system is widely thought to have evolved to protect the host from microbial infection; however, studies of GF animals have shown that the microbiota is, in fact, critical for full maturation of the intestinal immune system. GF animals have smaller Peyer's

Antimicrobial peptides

Paneth cells are specialized epithelial cells situated at the base of the small-intestinal crypts that produce most of the antimicrobial peptides in the small intestine [26]. Microbial colonization of GF mice initiates expression of a complex antimicrobial transcriptional program, which is dependent on MyD88-dependent TLR activation. Since Paneth cell–MyD88 signaling also plays a role in limiting intestinal barrier penetration by commensal and pathogenic bacteria upon oral gavage, investigators

IgA

The intestinal mucosa contains abundant IgA-secreting plasma cells, and secreted IgA can play a role in host defense against pathogens. Recent studies have revealed that IgA is also a critical component in regulating gut homeostasis. Intestinal dendritic cells (DCs) can retain small numbers of live commensals, which allows DCs to selectively induce IgA resulting in protection against mucosal penetration by commensals [38]. GF mice have greatly reduced numbers of IgA-secreting plasma cells, but

Conclusions

The human gut harbors nearly 100 trillion intestinal bacteria and numerous foreign food antigens that are beneficial to the microbe and the host. However, these components of the microbiota can also pose a threat to the host. Here, we have discussed various immunologic mechanisms crucial for maintaining homeostasis in the gut. The regulation of many of these mechanisms by the commensal microbiota reflects the strong symbiotic relationship that has evolved between the microbiota and its host.

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