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

Science Advances
X TangZ Zhang

Abstract

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.

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Citations

Jun 10, 2020·Bulletin of the National Research Centre·Manal A Hamed
Oct 6, 2020·Frontiers in Immunology·Isaac M Barber-AxthelmJennifer A Juno
Sep 26, 2020·Frontiers in Immunology·Alexandra J CorbettZhenjun Chen
Sep 10, 2020·Frontiers in Immunology·Melina IoannidisMariolina Salio
Apr 10, 2020·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Juanjuan ZhaoZheng Zhang
Dec 29, 2020·Molecular Immunology·Huimeng WangAlexandra J Corbett
Dec 24, 2020·Trends in Microbiology·Edwin LeeansyahJohan K Sandberg
Aug 29, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Qianting YangZheng Zhang

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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
FACS
flow cytometry
scRNAseq
enzyme-linked immunosorbent assay
ELISA
bronchoalveolar lavage
Assay
PCA

Software Mentioned

BD Rhapsody
MAST
UMAP
Abseq
Seurat
Prism
DAVID
GraphPad
FlowJo

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