Role of the innate immune system in systemic enterococcus dissemination and clearance

Abstract

Enterococci are gram-positive commensals of the mammalian intestinal tract and intrinsically resistant to broad-spectrum cephalosporin antibiotics. They proliferate in the gut and disseminate systemically causing infections in immunocompromised individuals and hospitalized patients undergoing cephalosporin therapy. Using a unique mouse model with stable intestinal colonization with a lab strain of Enterococcus faecalis (EF), we investigated the role of the immune system in EF dissemination and clearance from mice treated with cephalosporins. Ceftriaxone mediated depletion of indigenous microbiota was associated with expansion of EF throughout the gut, reduced levels of gut mucosal barrier components and eventually EF dissemination to peripheral organs. We observed that EF was not associated with the FACS sorted populations of lamina propria mononuclear phagocytes suggesting that these immune cells did not actively translocate EF across the intestinal mucosa. Mice cleared EF systemically by 2 weeks post-antibiotic treatment without evidence of adaptive immune response. Studies in Rag1−/− mice suggested that adaptive immune system was not essential in EF clearance or containment. Our observations support that intestinal containment and systemic clearance of EF are mediated by innate immune mechanisms. We predict that this reflects general mechanisms for host containment and management of the intestinal commensal microbiota.