Heterogeneous responses of mucosal-associated invariant T cells to mycobacteria and E.coli
Manju Sharma, Shuangmin Zhang, Liang Niu, Xiang Zhang, Shouxiong Huang*
Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH 45267
*Immunobiology graduate program, Cincinnati Children’s Hospital, Cincinnati, OH 45267
Mucosal-associated invariant T (MAIT) cells as innate-like T cells rapidly respond to mycobacteria. Animal studies demonstrated that MAIT cells are protective against mycobacteria at the early stage of infections. However, the MAIT cell activation program responding to mycobacteria has not been fully understood. To determine whether MAIT cells respond to mycobacterial infections as divergent from other bacteria, we determined the surface markers, transcriptomic profiles, and effector responses of activated human MAIT cells upon the stimulation of mycobacteria and E.coli. Results revealed that bacterial-incubated antigen-presenting cells stimulated abundant human CD8+ MAIT cells to upregulate the co-expression of CD69 and CD26. Transcriptomic analyses revealed that CD69+CD26++ CD8+MAIT cells highly expressed numerous genes potentially inducing anti-mycobacterial immune responses, such as pro-inflammatory cytokines, cytolytic molecules, NK cell receptors, and transcription factors, in contrast to inactivated counterparts CD69+/-CD26+/- CD8+MAIT cells. Moreover, mycobacteria distinctively stimulated intracellular signaling and effector pathways from the stimulation of E.coli. Flow cytometry detected that activated CD8+MAIT cells produced TNFa, IFNg, and granulysin to inhibit mycobacterial growth and fight mycobacterial infection. Together, results strongly support that CD8+MAIT cells differentially respond to mycobacterial and E.coli stimulations to elicit innate-like anti-mycobacterial immune responses.