Clec12a controls colitis by tempering inflammation and restricting expansion of specific commensals.

Abstract

Microbiota composition regulates colitis severity, yet the innate immune mechanisms that control commensal communities and prevent disease remain unclear. We show that the innate immune receptor, Clec12a, impacts colitis severity by regulating microbiota composition. Transplantation of microbiota from a Clec12aanimal is sufficient to worsen colitis in wild-type mice. Clec12amice have expanded Faecalibaculum rodentium, and treatment with F. rodentium similarly exacerbates disease. However, Clec12aanimals are resistant to colitis development when rederived into an 11-member community, underscoring the role of specific species. Colitis in Clec12amice is dependent on monocytes, and cytokine and sequencing analysis in Clec12amacrophages and serum shows enhanced inflammation with a reduction in phagocytic genes. F. rodentium specifically binds to Clec12a, and Clec12a-deficient macrophages are impaired in their ability to phagocytose F. rodentium. Thus, Clec12a contributes to an innate-immune-surveillance mechanism that controls the expansion of potentially harmful commensals while limiting inflammation.