@article{5f2bcdb4e82b4eaa9b088bc93de41ac2,
title = "MR1-Restricted MAIT Cells From The Human Lung Mucosal Surface Have Distinct Phenotypic, Functional, and Transcriptomic Features That Are Preserved in HIV Infection",
abstract = "Mucosal associated invariant T (MAIT) cells are a class of innate-like T cells that utilize a semi-invariant αβ T cell receptor to recognize small molecule ligands produced by bacteria and fungi. Despite growing evidence that immune cells at mucosal surfaces are often phenotypically and functionally distinct from those in the peripheral circulation, knowledge about the characteristics of MAIT cells at the lung mucosal surface, the site of exposure to respiratory pathogens, is limited. HIV infection has been shown to have a profound effect on the number and function of MAIT cells in the peripheral blood, but its effect on lung mucosal MAIT cells is unknown. We examined the phenotypic, functional, and transcriptomic features of major histocompatibility complex (MHC) class I-related (MR1)-restricted MAIT cells from the peripheral blood and bronchoalveolar compartments of otherwise healthy individuals with latent Mycobacterium tuberculosis (Mtb) infection who were either HIV uninfected or HIV infected. Peripheral blood MAIT cells consistently co-expressed typical MAIT cell surface markers CD161 and CD26 in HIV-negative individuals, while paired bronchoalveolar MAIT cells displayed heterogenous expression of these markers. Bronchoalveolar MAIT cells produced lower levels of pro-inflammatory cytokine IFN-γ and expressed higher levels of co-inhibitory markers PD-1 and TIM-3 than peripheral MAIT cells. HIV infection resulted in decreased frequencies and pro-inflammatory function of peripheral blood MAIT cells, while in the bronchoalveolar compartment MAIT cell frequency was decreased but phenotype and function were not significantly altered. Single-cell transcriptomic analysis demonstrated greater heterogeneity among bronchoalveolar compared to peripheral blood MAIT cells and suggested a distinct subset in the bronchoalveolar compartment. The transcriptional features of this bronchoalveolar subset were associated with MAIT cell tissue repair functions. In summary, we found previously undescribed phenotypic and transcriptional heterogeneity of bronchoalveolar MAIT cells in HIV-negative people. In HIV infection, we found numeric depletion of MAIT cells in both anatomical compartments but preservation of the novel phenotypic and transcriptional features of bronchoalveolar MAIT cells.",
keywords = "HIV, lung mucosal immunity, mucosal associated invariant T cells, single-cell transcriptomics, tuberculosis",
author = "Sharon Khuzwayo and Maphe Mthembu and Meermeier, {Erin W.} and Prakadan, {Sanjay M.} and Kazer, {Samuel W.} and Thierry Bassett and Kennedy Nyamande and Khan, {Dilshaad Fakey} and Priya Maharaj and Mohammed Mitha and Moosa Suleman and Zoey Mhlane and Dirhona Ramjit and Farina Karim and Shalek, {Alex K.} and Lewinsohn, {David M.} and Thumbi Ndung{\textquoteright}u and Wong, {Emily B.}",
note = "Funding Information: We would like to thank the study participants and the clinical staff of Inkosi Albert Luthuli Hospital, without whom this work would not be possible. We would also like to thank the AHRI Immunology core, the OHSU Flow Cytometry core, the AHRI Biorepository, Clinical and Microbiology cores. The MR1 tetramer technology was developed jointly by Dr James McCluskey, Dr Jamie Rossjohn, and Dr David Fairlie, and the material was produced by the NIH Tetramer Core Facility as permitted to be distributed by the University of Melbourne. Funding Information: This study was supported by the NIAID/NIH (K08AI118538 to EW and a collaborative award from the Harvard Center for AIDS Research 5P30AI060354-12 (to EW, TN,and AS), the Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative [grant no. DEL-15-006]. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS){\textquoteright}s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa{\textquoteright}s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust [grant no. 107752/Z/15/Z] and the UK government (to SK and MMt); and additional support was received through the South African National Research Foundation Freestanding, Innovation and Scarce Skills Development Fund (to SK). The study was also supported in part by the Strategic Health Innovation Partnerships (SHIP) Unit of the South African Medical Research Council with funds received from the South African Department of Science and Innovation as part of a bilateral research collaboration agreement with the Government of India (to TN). Other support came from the South African Research Chairs Initiative and the Victor Daitz Foundation. AS was Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2021 Khuzwayo, Mthembu, Meermeier, Prakadan, Kazer, Bassett, Nyamande, Khan, Maharaj, Mitha, Suleman, Mhlane, Ramjit, Karim, Shalek, Lewinsohn, Ndung{\textquoteright}u and Wong.",
year = "2021",
month = apr,
day = "9",
doi = "10.3389/fimmu.2021.631410",
language = "English (US)",
volume = "12",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",
}