Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria

Abstract

SUMMARY The gastrointestinal tract of mammals is inhabited by hundreds of distinct species of commensal microorganisms that exist in a mutualistic relationship with the host. How commensal microbiota influence the host immune system is poorly understood. We show here that colonization of the small intestine of mice with a single commensal microbe, segmented filamentous bacterium (SFB), is sufficient to induce the appearance of CD4+ T helper cells that produce IL-17 and IL-22 (Th17 cells) in the lamina propria. SFB adhere tightly to the surface of epithelial cells in the terminal ileum of mice with Th17 cells but are absent from mice that have few Th17 cells. Colonization with SFB was correlated with increased expression of genes associated with inflammation and anti-microbial defenses, and resulted in enhanced resistance to the intestinal pathogen Citrobacter rodentium. Thus, manipulation of this commensalregulated pathway may provide new opportunities for enhancing mucosal immunity and treating autoimmune disease.

Moving beyond microbiome-wide associations to causal microbe identification

“…The previous demonstration that SFB induces Reg3γ expression in GF and SPF mice confirms the more general applicability of results obtained using our specific gnotobiotic mice 8 . Our requirement that organisms be unchanged between MMb and MMb HMb-1d mice correctly excluded a relation between Reg3γ expression and Lactobacillus vaginalis , a close relative of L. reuteri that is also absent in HMb mice (Extended Data Fig 6).…”

“…In both cases, the sheer number of implicated microbes makes prioritizing and pursuing potential leads extremely challenging. Focusing on some of the most differentially abundant organisms detected in MWAS has identified some of the few microbes that have been causally related to a phenotype 8 . Using this approach in HMb and MMb mice, we identified 26 taxa present in one group and absent in the other.…”

The regulation of host defences to infection by the microbiota

“…This hypothesis is supported by a study showing that mice with segmented filamentous bacteria (SFB) in the gastrointestinal tract survive Staphylococcus aureus pneumonia better than those without 61. SFB are known to regulate T‐cell differentiation in the murine intestine, which protects against intestinal infection,47 but this new work demonstrates that SFB also play a wider role in enhancing extra‐intestinal host defences. After intranasal infection with methicillin‐resistant Staphylococcus aureus , SFB‐negative mice had higher bacterial burdens in the lung and spleen, compared with SFB‐positive mice 61.…”

Functional and phenotypic heterogeneity of group 3 innate lymphoid cells

“…Mice with disrupted ILC3‐derived IL‐22 responses exhibit altered gut microbiota and increased susceptibility to experimentally induced colitis 49, 80, 81, 82. Most notably, expansion of segmented filamentous bacteria (SFB) – a canonical Th17‐inducing commensal species – occurs in the absence of ILC3 responses 49.…”