Regulation of Th17 CD4 T Cell Responses During Pulmonary Group A Streptococcus (GAS) Infections by Dendritic cells

Abstract

Abstract The respiratory mucosa serves as the first line of cellular immune defense against respiratory pathogen exposure. Prior to the use of antibiotics, GAS accounted for 2–5% of pulmonary bacterial infections and has been associated with secondary bacterial pneumonia following influenza virus infections particularly during pandemics. While studies examining the immune response within the lower airways of the lung during GAS pneumonia have been limited, current findings suggest that nasal infections that elicit both Th17 and antibody (Ab) responses reduce disease and colonization. Given the role that local dendritic cell (DC): T cell interactions within the lungs have been demonstrated to have in other infections, our hypothesis is that pulmonary DC contribute to protective Th17 CD4 T cell responses during GAS infections. Our findings suggest that GAS infection induces the recruitment of a novel dendritic cell subset into the lungs from the blood whose accumulation correlates with local Th17 responses. Depletion of the DC subset results in reduced pulmonary Th17 responses and increased mortality. Therefore, our result suggest that this DC subset is critical for local Th17 responses and control of pulmonary GAS infections. An improved understanding of the contribution of these DC to the regulation of Th17 and other CD4 T cell responses during GAS infection may allow targeted therapy to boost and shape the local CD4 T cell response and anti-GAS immunity.