UC San Diego

The NOD signaling pathway mediates innate immunity through the detection of pathogens in the host system. NOD1 and NOD2 both contain a caspase activation and recruitment domain that interacts with RIP2, leading to the activation of the transcription factor NFkB. However, their roles in otitis media have yet to be examined. We investigated experimental otitis media in wild-type and RIP2-/- mice inoculated in the middle ear with non-typeable Haemophilus influenzae. Compared to the wild-type, RIP2-/- mice showed persistent middle ear infection up to 21 days. This included prolonged mucosal hyperplasia and leukocytic infiltration, which were especially severe in RIP2- deficient mice. Recruitment of neutrophils and macrophages were also substantially delayed. In addition to inflammation, viable bacteria could be cultured in RIP2-/- mice for much longer than in wild-type mice, suggesting that an inability to clear bacterial infection may underlie the persistent nature of otitis media in these mice. These results demonstrate that the NOD-like receptor adaptor RIP2 plays a significant role in the innate immune host response in the middle ear