Mucosal-associated Invariant T (MAIT) cells populate barrier tissues including the lungs in which they contribute to defense against respiratory infections. While MAIT cells have been involved in host resistance to infections caused by Gram-negative bacteria, their endogeneous contribution in immunity against Gram-positive bacteria-driven pneumonia is still an enigma.
Our study demonstrates that both mouse and human MAIT cells activate during severe infection caused by Streptococcus pneumoniae, the leading cause of community-acquired bacterial pneumonia. Upon infection, lung MAIT cells undergo a prompt transcriptional reprogramming associated with a potent antimicrobial signature. Lung MAIT cell activation in this model relies on both TCR-dependent signals and activating cytokines that are timely controlled. Moreover, our data indicated an advantage in host resistance to pneumococcus in B6-MAITCAST mice as compared to B6 and B6-MAITCAST x Mr1-/- mice. Higher susceptibility in these latter was associated with uncontrolled bacterial outgrowth and dissemination, increased weight loss and impaired antibacterial activity of neutrophils.
Our works also indicate that prophylactic instillation of 5-OP-RU in both B6 and B6-MAITCAST mice is instrumental to confer full protection against lethal S. pneumoniae infection. The mechanisms involved in this protective effect will be presented.
These findings reveal that MAIT cells are new key cellular actors during Gram-positive bacterial infections.