NOD1/NOD2-mediated recognition of non-typeable Haemophilusinfluenzae activates innate immunity during otitismedia

摘要

Pathogen recognition following infection in mammals depends mainly on TLRs andNLRs. Herein, we evaluate the role of NOD1 and NOD2 signaling in theinflammatory responses of the middle ear (ME) mucosa and leukocytes recruitmentto infection site during otitis media (OM). OM is a common pediatric diseasewith prevalent repercussions on hearing health. While many risk factors havebeen implicated to OM proneness, immunity and the triggering of inflammation arecentral to OM pathology. We observed that many genes encoding members of the NODleucine-rich repeat and their downstream adaptor/effector molecules werestrongly regulated during the course of OM. When compared to wild type C57BL/6mice, NOD1- and NOD2-deficient mice were susceptible to prolonged OM infectionby non-typeable . NOD1-deficient miceappeared to have reduced macrophage enlistment with a delayed inflammatoryresponse by neutrophils and prolonged mucosal hyperplasia, whereas NOD2knockouts exhibited an overall reduction in the number of leukocytes recruitedto the ME, leading to delayed bacterial clearance. Altogether, these data showthat the NODs play a role in the pathogenesis and recovery of OM and reinforcethe importance of innate immune signaling in the protective host response.