Microbiota exposure following DSS-induced colitis promotes Mincle-mediated training of myeloid progenitors

Impairment of the intestinal barrier allows the systemic translocation of commensal bacteria, inducing a pro-inflammatory state in the host. To explore this link, we investigated innate immune responses following increased gut permeability upon administration of dextran sulfate sodium (DSS) in mice. We found that microbiota translocation induced trained immunity (TI) in mouse myeloid bone marrow progenitors (BMPs). Enterococcus faecalis was isolated from bone marrow following DSS treatment and induced trained immunity hallmarks in bone marrow-derived mouse macrophages and human monocytes. Notably, DSS treatment or heat-killed E. faecalis reprogrammed BMPs, resulting in enhanced inflammatory responses in vitro and in vivo, and protection against pathogen infections. The C-type lectin receptor Mincle (Clec4e) was essential for E. faecalis-induced TI in BMPs. Clec4e-/- mice showed impaired TI upon E. faecalis and reduced pathology following DSS treatment. Thus, Mincle sensing of E. faecalis induces TI that may contribute to pathologies associated with increased gut permeability. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series