Understanding the Role of Mucosal-Associated Invariant T-Cells in Non-human Primate Models of HIV Infection

Abstract

Chronic HIV infection causes systemic immune activation and dysregulation, resulting in the impairment of most T-cell subsets including MAIT cells. Multiple human cohort studies demonstrate MAIT cells are selectively depleted in the peripheral blood and lymphoid tissues during HIV infection, with incomplete restoration during suppressive antiretroviral therapy. Because MAIT cells play an important role in mucosal defense against a wide array of pathogens, fully reconstituting the MAIT cell compartment in ART-treated populations could improve immunity against co-infections. Non-human primates (NHPs) are a valuable, well-described animal model for HIV infection in humans. NHPs also maintain MAIT cell frequencies more comparable to humans, compared to other common animal models, and provide a unique opportunity to study MAIT cells in the circulation and mucosal tissues in a longitudinal manner. Only recently, however, have NHP MAIT cells been thoroughly characterized using macaque-specific MR1 tetramer reagents. Here we review the similarities and differences between MAIT cells in humans and NHPs as well as the impact of SIV/SHIV infection on MAIT cells and the potential implications for future research.

Mucosal-associated invariant T cells in cancer: dual roles, complex interactions and therapeutic potential

“…MAIT cells have also been implicated in the immune response during viral infections such as COVID-19 and HIV infections. In the context of HIV infection, MAIT cells are depleted early on, but they retain functional cytokine expression, suggesting a potential role in controlling microbial translocation in the gut during HIV infection ( 34 , 44 ). Additionally, MAIT cells have been shown to respond to and suppress HIV-1, suggesting an antiviral protective role in vivo ( 45 ).…”

Mucosal-Associated Invariant T Cells in the Digestive System: Defender or Destroyer?

“… 6 , 11 , 12 , 13 , 19 , 20 , 21 , 22 , 23 , 24 , 25 Nonhuman primates do not have as many MAIT cells as humans, but their distribution in the liver and mucosal tissues is similar to that of humans. 26 The frequency of MAIT cells in commonly used laboratory mice (C57BL/6J and BALB/c) is much lower than in humans. 11 , 12 , 21 However, the frequency of MAIT cells was 20-fold higher in wild mice captured in Thailand than C57BL/6J mice.…”

Mucosal‐associated invariant T cells: A cryptic coordinator in HIV‐infected immune reconstitution

“…Recently, MAIT cells have gained attention during HIV infection, especially as they are a key component of mucosal immunity, and their alteration during HIV infection may play a critical role in intestinal microbial homeostasis, immune activation, and immune reconstitution in HIV‐infected patients 132‐134 …”

“…Recently, MAIT cells have gained attention during HIV infection, especially as they are a key component of mucosal immunity, and their alteration during HIV infection may play a critical role in intestinal microbial homeostasis, immune activation, and immune reconstitution in HIV-infected patients. [132][133][134] The population of MAIT cells is significantly decreased and their function is severely impaired during HIV infection, which is difficult to restore despite effective treatment. 16,17 A study by Leeansyah et al 135 revealed the cytolytic capacity and cytokine production of MAIT cells to be severely defective in HIV-1-infected patients, in association with downregulation of the transcription factors T-bet and Eomes.…”