Th17 Cytokines and the Gut Mucosal Barrier

Local immune responses serve to contain infections by pathogens to the gut while preventing pathogen dissemination to systemic sites. Several subsets of T cells in the gut (T-helper 17 cells, γδ T cells, natural killer (NK), and NK-T cells) contribute to the mucosal response to pathogens by secreting a subset of cytokines including interleukin (IL)-17A, IL-17F, IL-22, and IL-26. These cytokines induce the secretion of chemokines and antimicrobial proteins, thereby orchestrating the mucosal barrier against gastrointestinal pathogens. While the mucosal barrier prevents bacterial dissemination from the gut, it also promotes colonization by pathogens that are resistant to some of the inducible antimicrobial responses. In this review, we describe the contribution of Th17 cytokines to the gut mucosal barrier during bacterial infections

How nutrition and the maternal microbiota shape the neonatal immune system.

The mucosal surfaces of mammals are densely colonized with microorganisms that are commonly referred to as the commensal microbiota. It is believed that the fetus in utero is sterile and that colonization with microorganisms starts only after birth. Nevertheless, the unborn fetus is exposed to a multitude of metabolites that originate from the commensal microbiota of the mother that reach systemic sites of the maternal body. The intestinal microbiota is strongly personalized and influenced by environmental factors, including nutrition. Members of the maternal microbiota can metabolize dietary components, pharmaceuticals and toxins, which can subsequently be passed to the developing fetus or the breast-feeding neonate. In this Review, we discuss the complex interplay between nutrition, the maternal microbiota and ingested chemicals, and summarize their effects on immunity in the offspring

Immune responses that adapt the intestinal mucosa to commensal intestinal bacteria

Animals contain an enormous load of non-pathogenic bacteria in the lower intestine, which exploit an environment with a stable temperature and abundant carbon sources. Our load of bacteria outnumbers our own cells. In order to survive with such a high number of organisms in very close proximity to host tissues the intestinal mucosa and its immune system is highly adapted. Mucosal immune responses are induced by small numbers of live commensal organisms penetrating the Peyer's patches and persisting in dendritic cells (DC). These DC can induce immunoglobulin A(+) (IgA(+)) B cells, which recirculate through the lymph and bloodstream to populate the lamina propria and secrete protective IgA. Because DC loaded with commensal bacteria do not penetrate further than the mesenteric lymph nodes, immune induction to commensals is confined to the mucosa, allowing strong mucosal immune responses to be induced whilst the systemic immune system remains relatively ignorant of these organisms

Immune adaptations that maintain homeostasis with the intestinal microbiota

Humans harbour nearly 100 trillion intestinal bacteria that are essential for health. Millions of years of co-evolution have moulded this human-microorganism interaction into a symbiotic relationship in which gut bacteria make essential contributions to human nutrient metabolism and in return occupy a nutrient-rich environment. Although intestinal microorganisms carry out essential functions for their hosts, they pose a constant threat of invasion owing to their sheer numbers and the large intestinal surface area. In this Review, we discuss the unique adaptations of the intestinal immune system that maintain homeostatic interactions with a diverse resident microbiota