Sectm1a Depletion Promotes Neutrophil Recruitment during Pneumococcal Pneumonia

Airway epithelial cells (AECs) play an essential role in the immune response during bacterial pneumonia. Secreted and transmembrane 1a (Sectm1a) is specifically expressed in AECs during early <i>Streptococcus pneumoniae</i> (SP) infection. However, its function remains largely unexplored. Here, we aimed to clarify the function of Sectm1a during serotype 3 pneumococcal pneumonia primarily using an <i>in vivo</i> mouse model. Our findings showed that Type I IFNs directly induced Sectm1a expression in AECs. Sectm1a depletion in an <i>in vivo</i> mouse model improved survival rate and enhanced the clearance of intrapulmonary bacterial burden at an early stage of SP infection. Correspondingly, Sectm1a depletion increased the count of intrapulmonary γδT cells, promoted IL-17A production by these cells, and enhanced intrapulmonary neutrophil responses against SP. Notably, IL-17A production in isolated lung γδT cells was directly suppressed by Sectm1a <i>ex vivo</i>. Furthermore, Sectm1a depletion altered the migration and activation markers of γδT cells <i>in vivo</i>, indicating that the AEC-derived Sectm1a is associated with the phenotypes of γδT cells. These findings suggest that Type I IFNs may play an important role through AEC-derived Sectm1a in this model, and Sectm1a signaling modulates excessive neutrophil inflammation and influences bacterial clearance by directly altering γδT cell functions during pneumococcal pneumonia. In summary, this study demonstrates that the Type I IFN-Sectm1a pathway could be a potential target to modify the acute response to bacterial pneumonia.