Human MAIT cells respond to and suppress HIV-1.
Chansavath PhetsouphanhPrabhjeet PhaloraCarl-Philipp HacksteinJohn ThornhillC Mee Ling MunierJodi MeyerowitzLyle MurrayCloete van VuurenDominique GoedhalsLinnea DrexhageRebecca MooreQuentin J SattentauJeffrey Yw MakDavid P FairlieSarah FidlerAnthony D KelleherJohn FraterPaul KlenermanPublished in: eLife (2021)
Human MAIT cells sit at the interface between innate and adaptive immunity, are polyfunctional and are capable of killing pathogen infected cells via recognition of the Class IB molecule MR1. MAIT cells have recently been shown to possess an antiviral protective role in vivo and we therefore sought to explore this in relation to HIV-1 infection. There was marked activation of MAIT cells in vivo in HIV-1-infected individuals, which decreased following ART. Stimulation of THP1 monocytes with R5 tropic HIV BAL potently activated MAIT cells in vitro. This activation was dependent on IL-12 and IL-18 but was independent of the TCR. Upon activation, MAIT cells were able to upregulate granzyme B, IFNγ and HIV-1 restriction factors CCL3, 4, and 5. Restriction factors produced by MAIT cells inhibited HIV-1 infection of primary PBMCs and immortalized target cells in vitro. These data reveal MAIT cells to be an additional T cell population responding to HIV-1, with a potentially important role in controlling viral replication at mucosal sites.
Keyphrases
- induced apoptosis
- hiv infected
- cell cycle arrest
- antiretroviral therapy
- endoplasmic reticulum stress
- hepatitis c virus
- immune response
- endothelial cells
- computed tomography
- human immunodeficiency virus
- hiv aids
- magnetic resonance
- dendritic cells
- sars cov
- genome wide
- hiv testing
- men who have sex with men
- cell proliferation
- liver injury
- ulcerative colitis
- peripheral blood
- candida albicans
- contrast enhanced