Frontiers in Immunology (Jan 2021)
Integrin Alpha E (CD103) Limits Virus-Induced IFN-I Production in Conventional Dendritic Cells
- Vikas Duhan,
- Vikas Duhan,
- Vishal Khairnar,
- Vishal Khairnar,
- Simo Kitanovski,
- Thamer A. Hamdan,
- Thamer A. Hamdan,
- Andrés D. Klein,
- Andrés D. Klein,
- Judith Lang,
- Murtaza Ali,
- Tom Adomati,
- Hilal Bhat,
- Hilal Bhat,
- Sarah-Kim Friedrich,
- Fanghui Li,
- Philippe Krebs,
- Anthony H. Futerman,
- Marylyn M. Addo,
- Marylyn M. Addo,
- Marylyn M. Addo,
- Cornelia Hardt,
- Daniel Hoffmann,
- Philipp A. Lang,
- Karl S. Lang
Affiliations
- Vikas Duhan
- Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen, Germany
- Vikas Duhan
- Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
- Vishal Khairnar
- Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen, Germany
- Vishal Khairnar
- Dana-Farber Cancer Institute, Harvard University, Boston, MA, United States
- Simo Kitanovski
- Bioinformatics and Computational Biophysics, Faculty of Biology, University of Duisburg-Essen, Essen, Germany
- Thamer A. Hamdan
- Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen, Germany
- Thamer A. Hamdan
- Department of Medical Laboratories, Faculty of Health Sciences, American University of Madaba, Amman, Jordan
- Andrés D. Klein
- Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel
- Andrés D. Klein
- Centro de Genética y Genómica, Universidad Del Desarrollo Clínica Alemana de Santiago, Santiago, Chile
- Judith Lang
- Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen, Germany
- Murtaza Ali
- Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen, Germany
- Tom Adomati
- Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen, Germany
- Hilal Bhat
- Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen, Germany
- Hilal Bhat
- Center for Molecular Medicine Cologne, University Hospital Cologne, University of Cologne, Cologne, Germany
- Sarah-Kim Friedrich
- Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen, Germany
- Fanghui Li
- Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen, Germany
- Philippe Krebs
- Institute of Pathology, University of Bern, Bern, Switzerland
- Anthony H. Futerman
- Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel
- Marylyn M. Addo
- 0University Medical Center Hamburg-Eppendorf, Division of Infectious Diseases, 1st Department of Medicine, Hamburg, Germany
- Marylyn M. Addo
- 1German Center for Infection Research, partner site Hamburg-Lübeck-Borstel-Riemse, Hamburg, Germany
- Marylyn M. Addo
- 2Department of Clinical Immunology of Infectious Diseases, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany
- Cornelia Hardt
- Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen, Germany
- Daniel Hoffmann
- Bioinformatics and Computational Biophysics, Faculty of Biology, University of Duisburg-Essen, Essen, Germany
- Philipp A. Lang
- 3Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Karl S. Lang
- Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen, Germany
- DOI
- https://doi.org/10.3389/fimmu.2020.607889
- Journal volume & issue
-
Vol. 11
Abstract
Early and strong production of IFN-I by dendritic cells is important to control vesicular stomatitis virus (VSV), however mechanisms which explain this cell-type specific innate immune activation remain to be defined. Here, using a genome wide association study (GWAS), we identified Integrin alpha-E (Itgae, CD103) as a new regulator of antiviral IFN-I production in a mouse model of vesicular stomatitis virus (VSV) infection. CD103 was specifically expressed by splenic conventional dendritic cells (cDCs) and limited IFN-I production in these cells during VSV infection. Mechanistically, CD103 suppressed AKT phosphorylation and mTOR activation in DCs. Deficiency in CD103 accelerated early IFN-I in cDCs and prevented death in VSV infected animals. In conclusion, CD103 participates in regulation of cDC specific IFN-I induction and thereby influences immune activation after VSV infection.
Keywords
