Role and function of MR1-restricted MAIT cells during intestinal infection     — ASN Events
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  2. Session 8 - Microbial Immunity I
  3. Role and function of MR1-restricted MAIT cells during intestinal infection    

Role and function of MR1-restricted MAIT cells during intestinal infection     (#63)

Elodie Macho Fernandez* 1 , Mahantappa Halimani* 1 , Nathaniel S Barton 1 , Claudio Nunes-Alves 2 , Mary H Young 3 , Natacha Veerapen 3 , Gurdyal S Besra 3 , Samuel M Behar 4 , Laurent Gapin 2 , Manfred Brigl 1
  1. Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. *These authors contributed equally to this work.
  2. Department of Immunology, University of Colorado School of Medicine, Denver, CO, USA
  3. School of Biosciences, University of Birmingham, Edgbaston, Birmingham, UK
  4. Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA

MR1-restricted Mucosal-Associated Invariant T (MAIT) cells are prominently localized in gastro-intestinal (GI) mucosal tissues and recognize microbial vitamin metabolite antigens that are produced by both intestinal commensals and pathogens. However, very little is known about the role and function of MAIT cells during intestinal infection in vivo, which is in large part due to the low numbers of MAIT cells in common laboratory mouse strains. To elucidate the functions of MAIT cells in intestinal immunity, we have generated a novel traceable MAIT T cell receptor (TCR) retrogenic (Rg) mouse model. To this end, we isolated and cloned a mouse MR1-restricted MAIT TCR that recognizes antigens from Salmonella typhimurium and Citrobacter rodentium, generated a MAIT TCRα/β P2A fusion construct and expressed the MAIT TCR by retroviral transduction in vivo. Rg MAIT cells are predominantly DN, CD44hi, and express the transcription factors PLZF and RORγt. Rg MAIT cells are found in lymphoid and non-lymphoid organs, including in the liver and in the small and large intestine among lamina propria lymphocytes (LPL) and intestinal epithelial lymphocytes (IEL). Among IEL, a significant fraction of Rg MAIT cells expresses CD8αα. Thus, Rg MAIT cells display many features of primary mouse and human MAIT cells. Following stimulation in vitro and during Salmonella infection in vivo, Rg MAIT cells secrete IFN-γ, TNF-α, IL-17A, and IL-22. Efficient in vitro expression of IL-17A, and in particular IL-22, is dependent on stimulation with IL-1β and IL-23. In addition, adoptive transfer of Rg MAIT cells into wild-type recipient mice decreases bacterial burden during Salmonella infection. Together, these results suggest that MAIT cells play a protective role during intestinal infection, and further studies aim to define the mechanisms of activation, antigen presenting cells, effector functions, and target cells that are critical for the contributions of MAIT cells to protective intestinal immunity.