Mucosal-Associated Invariant T Cells are not susceptible in vitro to SARS-CoV-2 infection but accumulate into the lungs of COVID-19 patients.
Xiaobo Huang, Jonas Kantonen, Kirsten Nowlan, Ngoc Anh Nguyen, Suvi T Jokiranta, Suvi Kuivanen, Nelli Heikkilä, Shamita Mahzabin, Anu Kantele, Olli Vapalahti, Liisa Myllykangas, Santtu Heinonen, Mikko I Mäyränpää, Tomas Strandin, Eliisa Kekäläinen
Author Information
Xiaobo Huang: Translational Immunology Research Program, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland. Electronic address: xiaobo.huang@helsinki.fi.
Jonas Kantonen: Department of Pathology, University of Helsinki, Helsinki, Finland; Department of Pathology, HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland.
Kirsten Nowlan: Translational Immunology Research Program, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland.
Ngoc Anh Nguyen: Translational Immunology Research Program, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland.
Suvi T Jokiranta: Translational Immunology Research Program, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland.
Suvi Kuivanen: Department of Virology, Medicum, University of Helsinki, Helsinki, Finland; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, Germany.
Nelli Heikkilä: Translational Immunology Research Program, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Center of Vaccinology, University of Geneva, Geneva, Switzerland.
Shamita Mahzabin: Translational Immunology Research Program, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Anu Kantele: Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Meilahti Vaccine Research Center, MeVac, Infectious Diseases, Helsinki University and Helsinki University Hospital, Helsinki, Finland.
Olli Vapalahti: Division of Virology and Immunology, HUS Diagnostic Center, HUSLAB Clinical Microbiology, Helsinki, Finland; Zoonosis Unit, Department of Virology, Medicum, University of Helsinki, Helsinki, Finland; Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
Liisa Myllykangas: Department of Pathology, University of Helsinki, Helsinki, Finland; Department of Pathology, HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland.
Santtu Heinonen: New Children's Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Mikko I Mäyränpää: Department of Pathology, University of Helsinki, Helsinki, Finland; Department of Pathology, HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland.
Tomas Strandin: Zoonosis Unit, Department of Virology, Medicum, University of Helsinki, Helsinki, Finland.
Eliisa Kekäläinen: Translational Immunology Research Program, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland; Division of Virology and Immunology, HUS Diagnostic Center, HUSLAB Clinical Microbiology, Helsinki, Finland.
Prolonged T cell lymphopenia is common in COVID-19, caused by SARS-CoV-2. While the mechanisms of lymphopenia during COVID-19 remain elusive, it is especially pronounced in a specialized innate-like T cell population called Mucosal Associated Invariant T cells (MAITs). MAITs has been suggested to express Angiotensin-Converting Enzyme 2 (ACE2), which is the well-known cellular receptor for SARS-CoV-2. However, it is still unclear if SARS-CoV-2 can infect or affect MAIT cells directly. In this study, we performed multicolor flow cytometry on peripheral blood mononuclear cells obtained from COVID-19 patients to assess the frequencies of CD8Vα7.2CD161 MAIT subsets at acute and convalescent disease phases. The susceptibility of MAITs and T cells to direct exposure by SARS-CoV-2 was analysed using cells isolated from healthy donor buffy coats by viability assays, virus-specific RT-PCR, and flow cytometry. In situ lung immunofluorescence was used to evaluate retention of T cells, especially MAIT cells, in lung tissues during acute COVID-19. Our study confirms previous reports indicating that circulating MAITs are activated, and their frequency is declined in patients with acute SARS-CoV-2 infection, whereas an accumulation of MAITs and T cells was seen in the lung tissue of individuals with fatal COVID-19. However, despite a fraction of MAITs found to express ACE2, no evidence for the susceptibility of MAITs for direct infection or activation by SARS-CoV-2 particles was observed. Thus, their activation and decline in the circulation is most likely explained by indirect mechanisms involving other immune cells and cytokine-induced pro-inflammatory environment but not by direct exposure to viral particles at the infection site.
