Disruption of IL-17 signaling in the respiratory mucosa results in invasive streptococcal infection

Abstract

ABSTRACTStreptococcus pyogenesinfection of the upper respiratory tract and skin can lead to severe invasive streptococcal disease (ISD). Previous studies have demonstrated that the deficiency of IL-17 in mice (IL-17-/-) reduces mucosal immunity againstS. pyogenes. However, the impact of IL-17 deficiency on the development of ISD is unknown. Here, we model single or repeated non-lethal, intranasal (IN)S. pyogenesM1 strain infections in immunocompetent and IL-17-/-mice to assess bacterial dissemination following a final IN or skin challenge. Immunocompetent mice that received a singleS. pyogenesIN infection displayed long-lasting mucosal immunity and no systemic infection. However, in the absence of IL-17, a single IN infection resulted in the dissemination ofS. pyogenesto the spleens, which was further exacerbated by repeated IN infections. Interestingly, immunity following skin challenge did not show a correlation with IL-17 and was instead associated with the activation of germinal center responses and the accumulation of neutrophils in the spleen. Our results highlight the critical role of IL-17 in preventing ISD followingS. pyogenesinfection of the respiratory mucosa.