Iñaki Robles-Vera, Aitor Jarit-Cabanillas, Paola Brandi, María Martínez-López, Sarai Martínez-Cano, Manuel Rodrigo-Tapias, Marcos Femenía-Muiña, Ana Redondo-Urzainqui, Vanesa Nuñez, Cristina González-Correa, Javier Moleón, Juan Duarte, Laura Conejero, Pablo Mata-Martínez, Carmen María Díez-Rivero, Marta Bergón-Gutiérrez, Iván Fernández-López, Manuel J. Gómez, Ana Quintas, Ana Dopazo, David Sancho
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引用次数: 0
Abstract
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 that Enterococcus faecalis translocated 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-killed E. faecalis reprogrammed bone marrow progenitors (BMPs), resulting in enhanced inflammatory responses in vitro and in vivo and protection against subsequent 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 administration and reduced pathology following DSS treatment. Thus, Mincle sensing of E. faecalis induces TI that may have long-term effects on pathologies associated with increased gut permeability.
期刊介绍:
Immunity is a publication that focuses on publishing significant advancements in research related to immunology. We encourage the submission of studies that offer groundbreaking immunological discoveries, whether at the molecular, cellular, or whole organism level. Topics of interest encompass a wide range, such as cancer, infectious diseases, neuroimmunology, autoimmune diseases, allergies, mucosal immunity, metabolic diseases, and homeostasis.