AI Article Synopsis
- MAIT cells are significantly depleted in HIV-1 infected individuals, even with effective treatment, and this study investigates why.
- The research utilized various methods, including flow cytometry and RNA sequencing, to analyze MAIT cell characteristics in 127 HIV-1 patients, revealing that these cells show signs of high activation and increased pyroptosis (a form of inflammatory cell death).
- Findings indicate that aggravated pyroptosis in MAIT cells is linked to systemic T-cell activation and intestinal damage, and that proinflammatory cytokines are elevated in these patients, suggesting that the loss of MAIT cells potentially worsens HIV-1 disease progression.
Article Abstract
Background: Mucosal-associated invariant T (MAIT) cells are systemically depleted in human immunodeficiency virus type 1 (HIV-1) infected patients and are not replenished even after successful combined antiretroviral therapy (cART). This study aimed to identify the mechanism underlying MAIT cell depletion.
Methods: In the present study, we applied flow cytometry, single-cell RNA sequencing and immunohistochemical staining to evaluate the characteristics of pyroptotic MAIT cells in a total of 127 HIV-1 infected individuals, including 69 treatment-naive patients, 28 complete responders, 15 immunological non-responders, and 15 elite controllers, at the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
Results: Single-cell transcriptomic profiles revealed that circulating MAIT cells from HIV-1 infected subjects were highly activated, with upregulation of pyroptosis-related genes. Further analysis revealed that increased frequencies of pyroptotic MAIT cells correlated with markers of systemic T-cell activation, microbial translocation, and intestinal damage in cART-naive patients and poor CD4 T-cell recovery in long-term cART patients. Immunohistochemical staining revealed that MAIT cells in the gut mucosa of HIV-1 infected patients exhibited a strong active gasdermin-D (GSDMD, marker of pyroptosis) signal near the cavity side, suggesting that these MAIT cells underwent active pyroptosis in the colorectal mucosa. Increased levels of the proinflammatory cytokines interleukin-12 (IL-12) and IL-18 were observed in HIV-1 infected patients. In addition, activated MAIT cells exhibited an increased pyroptotic phenotype after being triggered by HIV-1 virions, T-cell receptor signals, IL-12 plus IL-18, and combinations of these factors, in vitro.
Conclusions: Activation-induced MAIT cell pyroptosis contributes to the loss of MAIT cells in HIV-1 infected patients, which could potentiate disease progression and poor immune reconstitution.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137088 | PMC |
| http://dx.doi.org/10.1186/s40779-022-00384-1 | DOI Listing |
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