Integrin Alpha E (CD103) Limits Virus-Induced IFN-I Production in Conventional Dendritic Cells.

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.

• Authors: Vikas Duhan, Vishal Khairnar, Simo Kitanovski, Thamer A Hamdan, Andrés D Klein, Judith Lang, Murtaza Ali, Tom Adomati, Hilal Bhat, Sarah-Kim Friedrich, Fanghui Li, Philippe Krebs, Anthony H Futerman, Marylyn M Addo, Cornelia Hardt, Daniel Hoffmann, Philipp A Lang, Karl S Lang
• Journal: Frontiers in immunology (Front Immunol) Vol. 11 Pg. 607889 ( 2020) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 33584680 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Duhan, Khairnar, Kitanovski, Hamdan, Klein, Lang, Ali, Adomati, Bhat, Friedrich, Li, Krebs, Futerman, Addo, Hardt, Hoffmann, Lang and Lang.

Chemical References

• Antigens, CD
• Ifnar1 protein, mouse
• Integrin alpha Chains
• Interferon Type I
• alpha E integrins
• Receptor, Interferon alpha-beta
• mTOR protein, mouse
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases

Topics

• Animals
• Antigens, CD (genetics, metabolism)
• Cells, Cultured
• Dendritic Cells (immunology, metabolism, virology)
• Disease Models, Animal
• Genome-Wide Association Study
• Host-Pathogen Interactions
• Immunity, Innate
• Integrin alpha Chains (genetics, metabolism)
• Interferon Type I (metabolism)
• Mice, 129 Strain
• Mice, Inbred AKR
• Mice, Inbred BALB C
• Mice, Inbred C3H
• Mice, Inbred C57BL
• Mice, Inbred DBA
• Mice, Inbred NOD
• Mice, Knockout
• Phosphorylation
• Proto-Oncogene Proteins c-akt (metabolism)
• Receptor, Interferon alpha-beta (genetics, metabolism)
• Signal Transduction
• TOR Serine-Threonine Kinases (metabolism)
• Vesicular Stomatitis (genetics, immunology, metabolism, virology)
• Vesiculovirus (growth & development, pathogenicity)
• Virus Replication