[S9-1] MAIT cell-directed therapy of Mycobacterium tuberculosis infection
Mycobacterium tuberculosis (Mtb) infection is a leading global cause of death due to infectious disease. Targeting mucosal-associated invariant T (MAIT) cells holds promise for the intervention strategies of tuberculosis (TB), but little is understood about the role of MAIT cells in host resistance to Mtb infection in vivo. In mice, we find that MAIT cells mount minimal responses after Mtb infection and MAIT cell-deficient MR1-/- mice display normal survival. However, treating mice with 5-OP-RU, a major MAIT cell antigen, during chronic infection drives MAIT cell expansion and enhances bacterial control, suggesting that post-exposure stimulation of MAIT cells may be a promising host-directed therapy for TB. To examine the potential therapeutic efficacy of 5-OP-RU treatment in a more relevant model of human TB, we treated Mtb infected rhesus macaques with 5-OP-RU. In contrast to mice, we find no therapeutic benefit observed with 5-OP-RU treatment of macaques with TB, MAIT cells do not expand in the tissues and rather become functionally impaired. Our study provides insight into basic in vivo MAIT cell biology and identifies a major barrier to the translatability of MAIT cell-directed therapies. The development of strategies to induce expansion of functional MAIT cells in macaques is needed to evaluate their clinical potential as targets of vaccines and therapeutics in humans.