IL-17A Promotes Pneumococcal Clearance By Recruiting Neutrophils And Inducing Apoptosis Through P38MAPK Dependent Mechanism In Acute Otitis Media

Streptococcus pneumoniae (S.pn) is a Gram-positive andhuman-restricted pathogen colonizing the nasopharynx in the absence ofclinical symptoms as well as a major pathogen causing Otitis media (OM) orPneumonia，both of them are the most common childhood infections. Uponbacterial infection, neutrophils are rapidly activated and recruited to theinfected site, acting as the front-line defender against emerging microbialpathogens via different ways. Evidence shows that interleukin17A (IL-17A),a neutrophil-inducing factor, plays important roles in immune response inseveral diseases. However, its function in response to S.pn OM remainsunclear. In this study, the function of IL-17A in response to S.pn OM wasexamined using an in vivo model. We developed a model of AOM inC57BL/6mice, and found neutrophils were the dominant immune cells thatinfiltrated to middle ear cavity (MEC) and contributed to the bacterialclearance. Using IL-17A KO mice, we found the IL-17A boosted neutrophilrecruitment to MEC and afterwards induced its apoptosis, which wereidentified to be conducive to bacterial clearance. In addition, our observation suggested that the p38MAPK signaling pathway was involved in therecruitment and apoptosis of neutrophils mediated by IL-17A. These datasupport the conclusion that IL-17A contributes to the host immune responseagainst S.pn by promoting neutrophil recruitment and apoptosis throughp38MAPK signaling pathway.