Th17 Cell Induction by Adhesion of Microbes to Intestinal Epithelial Cells

Abstract

SUMMARY Intestinal Th17 cells are induced and accumulate in response to colonization with a subgroup of intestinal microbes such as segmented filamentous bacteria (SFB) and certain extracellular pathogens. Here, we show that adhesion of microbes to intestinal epithelial cells (ECs) is a critical cue for Th17 induction. Upon monocolonization of germ-free mice or rats with SFB indigenous to mice (M-SFB) or rats (R-SFB), M-SFB and R-SFB showed host-specific adhesion to small intestinal ECs, accompanied by host-specific induction of Th17 cells. Citrobacter rodentium and Escherichia coli O157 triggered similar Th17 responses, whereas adhesion-defective mutants of these microbes failed to do so. Moreover, a mixture of 20 bacterial strains, which were selected and isolated from fecal samples of a patient with ulcerative colitis on the basis of their ability to cause a robust induction of Th17 cells in the mouse colon, also exhibited EC-adhesive characteristics.

Analysis of endoscopic brush samples identified mucosa-associated dysbiosis in inflammatory bowel disease

“…However, many of these studies relied on easily accessible fecal samples obtained on a single occasion, which may not properly represent mucosa-associated bacterial populations [17,18]. The mucosa-associated microbiota is considered to affect epithelial and mucosal function to a greater degree than luminal bacteria and to contribute more significantly to the pathogenesis of IBD [13,17,32].…”

The roles and functional mechanisms of interleukin-17 family cytokines in mucosal immunity

“…9 Recent studies also showed that IL-17D increased human NK cell cytotoxic functions in vitro and induced MCP-1 production in tumor endothelial cells to recruit NK cells for tumor rejection in vivo. 74 Moreover, the intestinal Th17 responses against Citrobacter rodentium required a physical interaction between the intestinal epithelial cells and the microbes, 75 indicating that both the recognition of MAMP molecules and the location of the microbes are critical for the generation of proper adaptive immune responses. Candida species are fungal species that frequently colonize the oral, intestinal, and vaginal surfaces and the skin of healthy individuals.…”

Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice

“…Similarly, a single bacterial strain, segmented filamentous bacteria (SFB), is sufficient to drive the accumulation of Th17 cells in the small-intestinal lamina propria (SI-LP) of mice (9,10); however, Th17-inducing microbes derived from the human gut have not yet been identified. A recent report did document an increase in colonic Th17 cells in GF mice inoculated with fecal material from healthy people and patients with ulcerative colitis, thus showing the existence of Th17-inducing species in the human microbiota (11). However, the microbiota composition differs substantially across both healthy individuals and colitis patients, and the symbionts responsible for Th17 cell induction at steady state remain uncharacterized (11).…”

“…A recent report did document an increase in colonic Th17 cells in GF mice inoculated with fecal material from healthy people and patients with ulcerative colitis, thus showing the existence of Th17-inducing species in the human microbiota (11). However, the microbiota composition differs substantially across both healthy individuals and colitis patients, and the symbionts responsible for Th17 cell induction at steady state remain uncharacterized (11).…”