Arming of MAIT Cell Cytolytic Antimicrobial Activity Is Induced by IL-7 and Defective in HIV-1 Infection

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The mucosa-associated invariant T (MAIT) cells recognize antigens that are byproducts of the riboflavin biosynthesis pathway shared by many microbes. These antigens are presented by the MHC class I-like MR1 molecules and trigger rapid activation of MAIT cells in an innate-like fashion with deployment of effector mechanisms including cytokine production and cytolysis. Here, we investigated the MAIT cell response to bacteria in humans infected with HIV-1, and possible means to restore functionality to these cells. MAIT cell dysfunction in HIV-infected patients included an inability to express components of the cytolytic effector machinery. Impairment of the MAIT cell population involved the loss of expression of the transcription factors T-bet and Eomes. Interestingly, IL-7 had strong effects on MAIT cells, including the antigen-independent arming of cytolytic function and enhanced sensitivity for low levels of bacteria. In HIV-infected patients, plasma IL-7 levels were positively associated with the size of the MAIT cell population, and IL-7 could rescue their function. These findings indicate that MAIT cell impairment in HIV-1 infection is broad-based, includes loss of critical transcription factors, and loss of cytolytic function. Furthermore, the data support the notion that IL-7 is a strong candidate for immunotherapy in diseases associated with MAIT cell loss.

Vyšlo v časopise: Arming of MAIT Cell Cytolytic Antimicrobial Activity Is Induced by IL-7 and Defective in HIV-1 Infection. PLoS Pathog 11(8): e32767. doi:10.1371/journal.ppat.1005072
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005072

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