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


Autoři: Amy L. Ellis aff001;  Alexis J. Balgeman aff001;  Erica C. Larson aff002;  Mark A. Rodgers aff002;  Cassaundra Ameel aff002;  Tonilynn Baranowski aff002;  Nadean Kannal aff001;  Pauline Maiello aff002;  Jennifer A. Juno aff003;  Charles A. Scanga aff002;  Shelby L. O’Connor aff001
Působiště autorů: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America aff001;  Department of Microbiology and Molecular Genetics, and Center for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America aff002;  Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia aff003
Vyšlo v časopise: MAIT cells are functionally impaired in a Mauritian cynomolgus macaque model of SIV and Mtb co-infection. PLoS Pathog 16(5): e1008585. doi:10.1371/journal.ppat.1008585
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008585

Souhrn

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 -naïve 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 TNFα when compared to SIV-naïve 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.

Klíčová slova:

Co-infections – Cytotoxic T cells – Flow cytometry – Granulomas – Macaque – Mycobacterium tuberculosis – SIV – T cells


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