Sustained IFN-I stimulation impairs MAIT cell responses to bacteria by inducing IL-10 during chronic HIV-1 infection

Sci Adv. 2020 Feb 19;6(8):eaaz0374. doi: 10.1126/sciadv.aaz0374. eCollection 2020 Feb.


Mucosal-associated invariant T (MAIT) cells in HIV-1-infected individuals are functionally impaired by poorly understood mechanisms. Single-cell transcriptional and surface protein analyses revealed that peripheral MAIT cells from HIV-1-infected subjects were highly activated with the up-regulation of interferon (IFN)-stimulated genes as compared to healthy individuals. Sustained IFN-α treatment suppressed MAIT cell responses to Escherichia coli by triggering high-level interleukin-10 (IL-10) production by monocytes, which subsequently inhibited the secretion of IL-12, a crucial costimulatory cytokine for MAIT cell activation. Blocking IFN-α or IL-10 receptors prevented MAIT cell dysfunction induced by HIV-1 exposure in vitro. Moreover, blocking the IL-10 receptor significantly improved anti-Mycobacterium tuberculosis responses of MAIT cells from HIV-1-infected patients. Our findings demonstrate the central role of the IFN-I/IL-10 axis in MAIT cell dysfunction during HIV-1 infection, which has implications for the development of anti-IFN-I/IL-10 strategies against bacterial coinfections in HIV-1-infected patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiretroviral Therapy, Highly Active
  • Costimulatory and Inhibitory T-Cell Receptors / metabolism
  • Cytokines / metabolism
  • Escherichia coli / immunology
  • Escherichia coli Infections / etiology
  • Female
  • HIV Infections / complications
  • HIV Infections / immunology*
  • HIV Infections / metabolism*
  • HIV Infections / virology*
  • HIV-1 / immunology
  • Host-Pathogen Interactions / immunology
  • Humans
  • Interferon Type I / metabolism*
  • Interleukin-10 / biosynthesis*
  • Lymphocyte Activation
  • Male
  • Mucosal-Associated Invariant T Cells / immunology*
  • Mucosal-Associated Invariant T Cells / metabolism*
  • Mucosal-Associated Invariant T Cells / virology*
  • Signal Transduction


  • Costimulatory and Inhibitory T-Cell Receptors
  • Cytokines
  • IL10 protein, human
  • Interferon Type I
  • Interleukin-10