Frontiers in Immunology (Oct 2023)
Macrophage migration inhibitory factor receptor CD74 expression is associated with expansion and differentiation of effector T cells in COVID-19 patients
- Jaana Westmeier,
- Annika Brochtrup,
- Krystallenia Paniskaki,
- Krystallenia Paniskaki,
- Zehra Karakoese,
- Tanja Werner,
- Kathrin Sutter,
- Kathrin Sutter,
- Sebastian Dolff,
- Andreas Limmer,
- Andreas Limmer,
- Daniela Mittermüller,
- Jia Liu,
- Jia Liu,
- Xin Zheng,
- Xin Zheng,
- Tetiana Koval,
- Igor Kaidashev,
- Marc Moritz Berger,
- Frank Herbstreit,
- Thorsten Brenner,
- Oliver Witzke,
- Mirko Trilling,
- Mirko Trilling,
- Mengji Lu,
- Mengji Lu,
- Dongliang Yang,
- Dongliang Yang,
- Nina Babel,
- Nina Babel,
- Timm Westhoff,
- Ulf Dittmer,
- Ulf Dittmer,
- Gennadiy Zelinskyy,
- Gennadiy Zelinskyy
Affiliations
- Jaana Westmeier
- Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Annika Brochtrup
- Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Krystallenia Paniskaki
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany
- Krystallenia Paniskaki
- Center for Translational Medicine, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, Germany
- Zehra Karakoese
- Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Tanja Werner
- Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Kathrin Sutter
- Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Kathrin Sutter
- Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology (HUST), Wuhan, China
- Sebastian Dolff
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany
- Andreas Limmer
- Department of Anesthesiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
- Andreas Limmer
- Department of Pediatric Heart Surgery, Friedrich-Alexander- Universität Erlangen-Nürnberg, Erlangen, Germany
- Daniela Mittermüller
- Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Jia Liu
- Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology (HUST), Wuhan, China
- Jia Liu
- Department of Infectious Diseases, Union Hospital of Tonji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China
- Xin Zheng
- Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology (HUST), Wuhan, China
- Xin Zheng
- Department of Infectious Diseases, Union Hospital of Tonji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China
- Tetiana Koval
- Department of Infectious Diseases with Epidemiology, Poltava State Medical University, Poltava, Ukraine
- Igor Kaidashev
- Department of Internal Medicine №3 with Phthisiology, Poltava State Medical University, Poltava, Ukraine
- Marc Moritz Berger
- Department of Anesthesiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
- Frank Herbstreit
- Department of Anesthesiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
- Thorsten Brenner
- Department of Anesthesiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
- Oliver Witzke
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany
- Mirko Trilling
- Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Mirko Trilling
- Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology (HUST), Wuhan, China
- Mengji Lu
- Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Mengji Lu
- Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology (HUST), Wuhan, China
- Dongliang Yang
- Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology (HUST), Wuhan, China
- Dongliang Yang
- Department of Infectious Diseases, Union Hospital of Tonji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China
- Nina Babel
- Center for Translational Medicine, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, Germany
- Nina Babel
- 0Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany
- Timm Westhoff
- 1Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr University of Bochum, Herne, Germany
- Ulf Dittmer
- Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Ulf Dittmer
- Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology (HUST), Wuhan, China
- Gennadiy Zelinskyy
- Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Gennadiy Zelinskyy
- Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology (HUST), Wuhan, China
- DOI
- https://doi.org/10.3389/fimmu.2023.1236374
- Journal volume & issue
-
Vol. 14
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused millions of COVID-19 cases and deaths worldwide. Severity of pulmonary pathologies and poor prognosis were reported to be associated with the activation non-virus-specific bystander T cells. In addition, high concentrations of the macrophage migration inhibitory factor (MIF) were found in serum of COVID-19 patients. We hypothesized that these two pathogenic factors might be related and analyzed the expression of receptors for MIF on T cells in COVID-19. T cells from PBMCs of hospitalized patients with mild and severe COVID-19 were characterized. A significantly higher proportion of CD4+ and CD8+ T cells from COVID-19 patients expressed CD74 on the cell surface compared to healthy controls. To induce intracellular signaling upon MIF binding, CD74 forms complexes with CD44, CXCR2, or CXCR4. The vast majority of CD74+ T cells expressed CD44, whereas expression of CXCR2 and CXCR4 was low in controls but increased upon SARS-CoV-2 infection. Hence, T cells in COVID-19 patients express receptors that render them responsive to MIF. A detailed analysis of CD74+ T cell populations revealed that most of them had a central memory phenotype early in infection, while cells with an effector and effector memory phenotype arose later during infection. Furthermore, CD74+ T cells produced more cytotoxic molecules and proliferation markers. Our data provide new insights into the MIF receptor and co-receptor repertoire of bystander T cells in COVID-19 and uncovers a novel and potentially druggable aspect of the immunological footprint of SARS-CoV-2.
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