Toll-like receptor ligands induce expression of the costimulatory molecule CD155 on antigen-presenting cells

PLoS One. 2013;8(1):e54406. doi: 10.1371/journal.pone.0054406. Epub 2013 Jan 17.

Abstract

Genotoxic stress and RAS induce the expression of CD155, a ligand for the immune receptors DNAM-1, CD96 and TIGIT. Here we show that antigen-presenting cells upregulate CD155 expression in response to Toll-like receptor activation. Induction of CD155 by Toll-like receptors depended on MYD88, TRIF and NF-κB. In addition, IRF3, but not IRF7, modulated CD155 upregulation in response to TLR3 signals. Immunization of CD155-deficient mice with OVA and the TLR9 agonist CpG resulted in increased OVA-specific IgG2a/c titers when compared to wild type mice. Splenocytes of immunized CD155-deficient mice secreted lower levels of IL-4 and fewer IL-4 and GATA-3 expressing CD4(+) T cells were present in the spleen of Cd155(-/-) mice. Our data suggest that CD155 regulates T(h)2 differentiation. Targeting of CD155 in immunization protocols using peptides may represent a promising new approach to boost protective humoral immunity in viral vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / metabolism
  • Animals
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Antigens, Differentiation, T-Lymphocyte / metabolism*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation
  • DNA Damage*
  • GATA3 Transcription Factor / metabolism
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology
  • Immunity, Humoral / genetics
  • Ligands
  • Mice
  • Myeloid Differentiation Factor 88 / metabolism
  • Receptors, Virus / genetics*
  • Receptors, Virus / immunology
  • Spleen / cytology
  • Spleen / metabolism
  • Th2 Cells* / cytology
  • Th2 Cells* / immunology
  • Th2 Cells* / metabolism
  • Toll-Like Receptor 3* / genetics
  • Toll-Like Receptor 3* / immunology
  • Viral Vaccines / immunology
  • Viral Vaccines / metabolism

Substances

  • Adaptor Proteins, Vesicular Transport
  • Antigens, Differentiation, T-Lymphocyte
  • CD226 antigen
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Ligands
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Receptors, Virus
  • TICAM-1 protein, mouse
  • TLR3 protein, mouse
  • Toll-Like Receptor 3
  • Viral Vaccines
  • poliovirus receptor

Grant support

This work was supported by the NRF grant HUJ-CREATE - Cellular and Molecular Mechanisms of Inflammation (http://www.nrf.gov.sg/nrf/default.aspx) and the NMRC grant NMRC/1158/2008 (http://www.nmrc.gov.sg/content/nmrc_internet/home.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.