Human MAIT cells respond to and suppress HIV-1

eLife

Sarah Fidler¹  John Frater¹  Prabhjeet Phalora²  David P Fairlie³  Anthony D Kelleher³  Linnea Drexhage⁴  Paul Klenerman⁵  C Mee Ling Munier⁵  Dominique Goedhals⁶  Carl-Philipp Hackstein⁷  Chansavath Phetsouphanh⁷  Cloete VanVuuren⁷  John Thornhill⁷  Lyle Murray⁷  Quentin J Sattentau⁸  Rebecca A Russell⁸  Jeffrey YW Mak⁸  Jodi Meyerowitz⁹ 

[1] ARC Centre of Excellence in Advanced Molecular Imaging, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia;The Kirby Institute, University of New South Wales, Sydney, Australia;ARC Centre of Excellence in Advanced Molecular Imaging, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia;Division of Virology, University of the Free State/National Health Laboratory Service, Free State, South Africa;Imperial College London, London, United Kingdom;Military Hospital, Bloemfontein, South Africa;Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom;Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom;The Kirby Institute, University of New South Wales, Sydney, Australia;

关键词: T cells;    MAIT cells;    HIV;    antiviral;    T cell response;   

DOI  :  10.7554/eLife.50324

来源: DOAJ

【 摘 要 】

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 HIVBAL 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.

【 授权许可】

Unknown