MR1-Restricted MAIT Cells From The Human Lung Mucosal Surface Have Distinct Phenotypic, Functional, and Transcriptomic Features That Are Preserved in HIV Infection
Year: 2021
Type: article
Study design: Observational Study
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 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 healthy 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 atypical MAIT cells and tissue repair functions. In summary, we found previously undescribed phenotypic and transcriptional heterogeneity of bronchoalveolar MAIT cells in healthy 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.
Source: Frontiers in Immunology
Authors: Sharon Khuzwayo, Maphe Mthembu, Erin W. Meermeier, Sanjay M. Prakadan, Samuel W. Kazer, Thierry Bassett, Kennedy Nyamande, Dilshaad Fakey Khan, Priya Maharaj, Mohammed Mitha, Moosa Suleman, Zoey Mhlane, Dirhona Ramjit, Farina Karim, Alex K. Shalek, David M. Lewinsohn, Thumbi Ndung’u, Emily B. Wong
Institutions: Africa Health Research Institute, University of KwaZulu-Natal, Oregon Health & Science University, Broad Institute, Harvard University, Ragon Institute of MGH, MIT and Harvard, Koch Institute for Integrative Cancer Research At MIT, Massachusetts Institute of Technology, Portland VA Medical Center, VA Portland Health Care System, Max Planck Institute for Infection Biology, University College London, University of Alabama at Birmingham, Massachusetts General Hospital
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
Funders: Oregon Health and Science University, Wellcome Trust, Government of the United Kingdom, Searle Scholars Program, Department of Science and Innovation, South Africa, National Research Foundation, South African Medical Research Council, University of Melbourne, New Partnership for Africa's Development, African Academy of Sciences, Victor Daitz Foundation, National Institutes of Health, Center for AIDS Research, University of Washington, Medical Research Council, Alliance for Accelerating Excellence in Science in Africa, National Institute of Allergy and Infectious Diseases
Awards: G2415674080, G3000957577, G4156438909, G4915094752, Sub-Saharan African Network for TB/HIV research Excellence (SANTHE), G5901762629, G6277005470, G6590892262, G6617178558, G6675272361, G6868616705, G7238354678, Studies of Mucosal Associated Invariant T (MAIT) cells in people with HIV, TB and HIV/TB co-infection in South Africa, G8119020889, G8183321107, G8445079486, G8488937646, G8547154903, Harvard University Center for AIDS Research, Sub-Saharan African Network for TB/HIV research Excellence (SANTHE)
OpenAlex ID: W3152660813