Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, New Haven, CT06510, USA
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06510, USA
Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA.
Toll-like receptors (TLRs) play a crucial role in host defense against microbial infection. The microbial ligands recognized by TLRs are not unique to pathogens, however, and are produced by both pathogenic and commensal microorganisms. It is thought that an inflammatory response to commensal bacteria is avoided due to sequestration of microflora by surface epithelia. Here, we show that commensal bacteria are recognized by TLRs under normal steady-state conditions, and this interaction plays a crucial role in the maintenance of intestinal epithelial homeostasis. Furthermore, we find that activation of TLRs by commensal microflora is critical for the protection against gut injury and associated mortality. These findings reveal a novel function of TLRsÑcontrol of intestinal epithelial homeostasis and protection from injuryÑand provide a new perspective on the evolution of host-microbial interactions.