Characterization of MR-1 tetramer-positive cells in a cynomolgus macaque model of M. tuberculosis/SIV coinfection (#79)
In HIV+ individuals, the most common cause of morbidity and mortality is co-infection with Mycobacterium tuberculosis (Mtb). Mucosal Associated Invariant T (MAIT) cells detect Mtb-derived metabolites presented by MR-1 molecules. The contribution of MAIT cells to controlling Mtb replication or whether their function is compromised by co-infection with HIV is relatively understudied. HIV/Mtb co-infections can be modeled in SIV/Mtb co-infected non-human primates, facilitating longitudinal analysis of MAIT cell phenotypes and functionality in blood and bronchoalveolar lavage fluid (BALF). Furthermore, individual TB granulomas can be collected at necropsy and assessed for the presence of MAIT cells as well.
In the present study, we infected SIV+ or SIV-naïve Mauritian cynomolgus macaques with Mtb and tested the hypothesis that SIV infection could alter the frequency and phenotypes of MR-1 restricted T cells in the peripheral blood. Animals were infected with a low dose (~10 CFU) Mtb Erdman strain for six weeks. The phenotype of peripheral blood MAIT cells was analyzed at this time. Animals co-infected with SIV had slightly higher frequencies of MAIT cells expressing the inhibitory markers PD1 and TIGIT, and lower frequencies of MAIT cells expressing the proliferation marker Ki-67. While this was a relatively small study, ongoing and future projects will elucidate changes in MAIT cells at higher doses of Mtb infection, as well as changes to MAIT cells in the BALF.
CD1-MR1 2017*