Translocation of gut Enterococcus faecalis trains myeloid bone marrow progenitors via the C-type lectin receptor Mincle

Impairment of the intestinal barrier allows the systemic translocation of commensal bacteria, inducing a pro-inflammatory state in the host. To address potential mechanisms underlying this link, we explored innate immune responses following increased gut permeability upon administration of dextran sulfate sodium (DSS) to mice. Microbiota translocation induced trained immunity (TI) in mouse myeloid bone marrow progenitors (BMPs). Enterococcus faecalis was the predominant bacteria detected in the bone marrow (BM) following DSS treatment. Notably, live or heat-killed E. faecalis induced reprogramming of mouse BMPs in vitro and in vivo and enhanced macrophage inflammatory activity, also training human monocytes. E. faecalis sensing by the C-type lectin receptor Mincle (Clec4e-/-) is essential for TI induction in BMPs. Consequently, Clec4e-/- mice showed impaired TI upon E. faecalis or reduced pathology following DSS treatment. Our results identify E. faecalis as inducer of TI-related inflammation that may contribute to pathologies associated with increased gut permeability.