Riboflavin Metabolism Variation Among Clinical Isolates of Streptococcus pneumoniae Results in Differential Activation of MAIT Cells.
Streptococcus pneumoniae is an important bacterial pathogen that causes a range of non-invasive and invasive diseases. The mechanisms underlying variability in the ability of S. pneumoniae to transition from nasopharyngeal colonization to disease-causing pathogen are not well-defined. Mucosal-associated invariant T (MAIT) cells are prevalent in mucosal tissues such as the airways and are thought to play an important role in the early response to infection with bacterial pathogens. The ability of MAIT cells to recognize and contain infection with S. pneumoniae is not known. In the present study, we analyzed MAIT cell responses to infection with clinical isolates of S. pneumoniae serotype 19A, a serotype linked to invasive pneumococcal disease. We found that while MAIT cells were capable of responding to human dendritic and airway epithelial cells infected with S. pneumoniae, the magnitude of response to different serotype 19A isolates was determined by genetic differences in the expression of the riboflavin biosynthesis pathway. MAIT cell release of cytokines correlated to differences in the ability of MAIT cells to respond to and control S. pneumoniae in vitro and in vivo in a mouse challenge model. Together, these results demonstrate first that there are genetic differences in riboflavin metabolism among clinical isolates of the same serotype, and second, that these likely determine MAIT cell function in response to infection with S. pneumoniae. These differences are critical in considering the role that MAIT cells play in early responses to pneumococcal infection and determining whether invasive disease will develop.