Human Gut Symbiont Promotes and Regulates Innate Immunity.

OBJECTIVE

is a flagellated gut anaerobic bacterium belonging to the family within the Firmicutes phylum. A significant decrease of colonization in the gut of ulcerative colitis patients has recently been demonstrated. In this work, we have investigated the mechanisms of -host cross talk using both murine and models.

DESIGN

The complete genome sequence of A2-183 was determined. C3H/HeN germ-free mice were mono-colonized with , and the host-microbe interaction was studied using histology, transcriptome analyses and FACS. Further investigations were performed and using the TLR5KO and DSS-colitis murine models.

RESULTS

In the bacterium, , host gut colonization upregulated genes involved in conjugation/mobilization, metabolism, motility, and chemotaxis. In the host cells, bacterial colonization upregulated genes related to antimicrobial peptides, gut barrier function, toll-like receptors (TLR) signaling, and T cell biology. CD4CD25FoxP3 T cell numbers increased in the of both mono-associated and conventional mice treated with . Treatment with the bacterium provided protection against DSS-induced colitis. The role of flagellin in host-bacterium interaction was also investigated.

CONCLUSION

Mono-association of mice with bacteria results in specific bidirectional gene expression patterns. A set of genes thought to be important for host colonization are induced in , while the host cells respond by strengthening gut barrier function and enhancing Treg population expansion, possibly TLR5-flagellin signaling. Our data reveal the immunomodulatory properties of that could be useful for the control and treatment of gut inflammation.