Riboflavin metabolism variation among clinical isolates of <em>Streptococcus pneumoniae</em> results in differential activation of MAIT cells   — ASN Events
  1. Schedule
  2. Session 3: Anti-microbial defense
  3. Riboflavin metabolism variation among clinical isolates of Streptococcus pneumoniae results in differential activation of MAIT cells  

Riboflavin metabolism variation among clinical isolates of Streptococcus pneumoniae results in differential activation of MAIT cells   (#24)

Curtis McMurtrey 1 , Nadine Hartmann 2 , Michelle Sorensen 3 , Joseph Mizgerd 4 , William Hildebrand 1 , Mitchell Kronenberg 2 , David Lewinsohn 5 6 , Melanie Harriff 5 6
  1. University of Oklahoma Health Sciences University, Oklahoma City
  2. La Jolla Institute for Allergy and Immunology, La Jolla
  3. Oregon Health & Sciences University, Portland, OR, USA
  4. Boston University School of Medicine, Boston
  5. VA Portland Health Care System, Portland, OR, USA
  6. Pulmonary and Critical Care Medicine, Oregon Health & Sciences University, Portland, OR, USA

Streptococcus pneumoniae is an important bacterial pathogen commonly causing a range of non-invasive and invasive diseases. The mechanisms underlying variability in the ability of distinct S. pneumococcus serotypes and genetic backgrounds to transition from nasopharyngeal colonization to disease-causing pathogen are not well-defined. Mucosal-associated invariant T (MAIT) cells are highly 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 tested the ability of human MAIT cells to respond to and control infection with a panel of clinical isolates of S. pneumoniae serotype 19A, a non-vaccine serotype linked to invasive pneumococcal disease. We found that while MAIT cells were capable of responding in vitro to human dendritic cells and airway epithelial cells infected with S. pneumoniae, the magnitude of response to cells infected with different serotype 19A isolates, determined by genetic differences in the expression of the riboflavin biosynthesis pathway. The differences in MAIT cell release of cytokines correlated to differences in the ability of MAIT cells to control S. pneumoniae in vitro and persisted in MAIT cells isolated from a mouse challenge model. Together, these results demonstrate that there are genetic differences in riboflavin metabolism among clinical isolates of the same serotype that 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.