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

Front Immunol. 2021 Jan 27:11:607889. doi: 10.3389/fimmu.2020.607889. eCollection 2020.

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: AKT; CD103; GWAS; IFN-I; Itgae; genome wide association screen; mTOR; vesicular stomatitis virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / virology*
  • Disease Models, Animal
  • Genome-Wide Association Study
  • Host-Pathogen Interactions
  • Immunity, Innate*
  • Integrin alpha Chains / genetics
  • Integrin alpha Chains / metabolism*
  • Interferon Type I / metabolism*
  • Mice
  • 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
  • Receptor, Interferon alpha-beta / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism
  • Vesicular Stomatitis / genetics
  • Vesicular Stomatitis / immunology
  • Vesicular Stomatitis / metabolism
  • Vesicular Stomatitis / virology*
  • Vesiculovirus / growth & development
  • Vesiculovirus / pathogenicity*
  • Virus Replication

Substances

  • 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