Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Department of Microbiology and Molecular Genetics, and Center for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
PLoS Pathog. 2020 May 20;16(5):e1008585. doi: 10.1371/journal.ppat.1008585. eCollection 2020 May.
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.
黏膜相关恒定 T（MAIT）细胞可以识别和响应某些细菌感染的细胞。几项结核分枝杆菌（Mtb）感染的体外和体内模型表明，MAIT 细胞可以有助于控制 Mtb，但这些研究通常是横断面的，并且使用外周血细胞。在早期 Mtb 感染期间，MAIT 细胞是否被招募到受 Mtb 影响的肉芽肿和淋巴结（LN）中，以及它们在那里可能起到什么作用，了解得还不够清楚。此外，HIV/SIV 感染是否会损害 Mtb 复制部位的 MAIT 细胞频率或功能尚未确定。使用毛里求斯食蟹猴（MCM），我们在感染 SIVmac239 之前和期间表型化了外周血和支气管肺泡灌洗（BAL）中的 MAIT 细胞。为了测试 SIV 合并感染是否会损害肉芽肿内 MAIT 细胞的频率和功能的假设，SIV+和-未感染的 MCM 用低剂量的 Mtb Erdman 感染，并在 Mtb 挑战后 6 周进行尸检。在 Mtb 感染的外周血、BAL 和受影响的淋巴结（LN）和肉芽肿中检查 MAIT 细胞的频率和功能。在单独感染 Mtb 的动物的肉芽肿内，MAIT 细胞未表达体内对 Mtb 反应的 T 细胞激活标志物。与 SIV 未感染的 MCM 相比，SIV 和 Mtb 合并感染导致激活/耗竭标志物 PD-1 和 TIGIT 的表达增加，并且分泌 TNFα 的能力降低。我们的研究提供了证据，表明 SIV 感染不会阻止 MAIT 细胞招募到 Mtb 感染部位，但确实会损害这些 MAIT 细胞的功能。它们受损的功能可能会对结核病疾病的长期控制产生直接或间接的影响。
