MAIT cells are functionally impaired in a Mauritian cynomolgus macaque model of SIV and Mtb co-infection.

Author summary MAIT cells are a population of immune cells that can directly detect and destroy some bacterially infected cells. Evidence suggests that MAIT cells may play a role in control of Mycobacterium tuberculosis (Mtb) infection, but few studies have examined MAIT cell activity within granulomas, which are the sites of Mtb replication. In addition, chronic HIV infection has been shown to impair the frequency and function of MAIT cells in humans, but these studies focus on peripheral blood and not the sites of Mtb infection. Here, we used a macaque model of SIV and Mtb co-infection to determine whether SIV, as a model for HIV, could dysregulate MAIT cells in tissues where Mtb replication is occurring. SIV co-infection did not affect the absolute numbers of MAIT cells present within granulomas but did impair the ability of the MAIT cells to respond to mycobacteria both in vivo and in vitro. Overall, our study provides evidence that SIV infection alters MAIT cells phenotypically, and impairs MAIT cell function. What effect this might have on antimycobacterial immunity is an avenue for future exploration. Mucosal-associated invariant T (MAIT) cells can recognize and respond to some bacterially infected cells. Several in vitro and in vivo models of Mycobacterium tuberculosis (Mtb) infection suggest that MAIT cells can contribute to control of Mtb, but these studies are often cross-sectional and use peripheral blood cells. Whether MAIT cells are recruited to Mtb-affected granulomas and lymph nodes (LNs) during early Mtb infection and what purpose they might serve there is less well understood. Furthermore, whether HIV/SIV infection impairs MAIT cell frequency or function at the sites of Mtb replication has not been determined. Using Mauritian cynomolgus macaques (MCM), we phenotyped MAIT cells in the peripheral blood and bronchoalveolar lavage (BAL) before and during infection with SIVmac239. To test the hypothesis that SIV co-infection impairs MAIT cell frequency and function within granulomas, SIV+ and -naive MCM were infected with a low dose of Mtb Erdman, and necropsied at 6 weeks post Mtb-challenge. MAIT cell frequency and function were examined within the peripheral blood, BAL, and Mtb-affected lymph nodes (LN) and granulomas. MAIT cells did not express markers indicative of T cell activation in response to Mtb in vivo within granulomas in animals infected with Mtb alone. SIV and Mtb co-infection led to increased expression of the activation/exhaustion markers PD-1 and TIGIT, and decreased ability to secrete TNF alpha when compared to SIV-naive MCM. Our study provides evidence that SIV infection does not prohibit the recruitment of MAIT cells to sites of Mtb infection, but does functionally impair those MAIT cells. Their impaired function could have impacts, either direct or indirect, on the long-term containment of TB disease.