Microbiota translocation following intestinal barrier disruption promotes Mincle-mediated training of myeloid progenitors in the bone marrow
Iñaki Robles-Vera et al.
Highlights
Gut barrier disruption induces trained immunity in bone marrow progenitors
Enterococcus faecalistranslocates to the bone marrow, inducing trained immunity
Mincle sensing ofE. faecalismediates trained immunity of bone marrow progenitors
Mincle-mediated trained immunity protects against infection but worsens inflammation
Summary
Impairment of the intestinal barrier allows the systemic translocation of commensal bacteria, inducing a proinflammatory state in the host. Here, we investigated innate immune responses following increased gut permeability upon administration of dextran sulfate sodium (DSS) in mice. We found thatEnterococcus faecalistranslocated to the bone marrow following DSS treatment and induced trained immunity (TI) hallmarks in bone-marrow-derived mouse macrophages and human monocytes. DSS treatment or heat-killedE. faecalisreprogrammed bone marrow progenitors (BMPs), resulting in enhanced inflammatory responsesin vitroandin vivoand protection against subsequent pathogen infections. The C-type lectin receptor Mincle (Clec4e) was essential forE. faecalis-induced TI in BMPs.Clec4e−/−mice showed impaired TI uponE. faecalisadministration and reduced pathology following DSS treatment. Thus, Mincle sensing ofE. faecalisinduces TI that may have long-term effects on pathologies associated with increased gut permeability.
