Specialized subsets of innate-like T cells and dendritic cells protect from lethal pneumococcal infection in the lung

Abstract

SummaryInnate-like T cells, including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells and γδ T cells, are present in various barrier tissues, including the lung. They carry out protective responses during infections, but the mechanisms for protection are not completely understood. Here, we investigated their roles during pulmonary infection with Streptococcus pneumoniae. Following infection, innate-like T cells rapidly increased in lung tissue, in part through recruitment, but TCR activation and cytokine production occurred mostly in IL-17-producing NKT17 and γδ T cells. NKT17 cells were preferentially located outside the vasculature prior to infection, as were CD103+ dendritic cells (cDC1), which were important both for antigen presentation to NKT17 cells and γδ T cell activation. Whereas IL-17A-producing γδ T cells also were numerous, GM-CSF was exclusive to NKT17 cells and contributed to iNKT cell-mediated protection. These studies demonstrate how particular cellular interactions and responses of functional subsets of innate-like T cells contribute to protection from pathogenic lung infection.