RNA sequencing of nasal lavage samples from mock- and Streptococcus pneumoniae-infected infant mice

Nasopharyngeal colonization by Streptococcus pneumoniae (Spn) is common and often asymptomatic, yet prolonged colonization increases the risk of transmission and invasive pneumococcal disease, particularly early in life. Host immune pathways that prevent persistent colonization remain poorly understood. Here, we examined how IL-1R and IL-17RA signaling shape host transcriptional responses during pneumococcal colonization of the upper respiratory tract. Using a mouse model of Spn colonization, we performed bulk RNA-sequencing on nasal lavages from mock-treated and Spn-colonized wild-type, Il1r1-/- and Il17ra-/- mice. In wild-type mice, colonization induced robust upregulation of inflammatory and innate immune gene programs, whereas many of these responses were attenuated in Il1r1-/- and Il17ra-/- mice. Taken together, this analysis demonstrates that IL-1R and IL-17RA signaling are required for full activation of host transcriptional responses that limit persistent Spn colonization.