Siglec-1 inhibits RSV-induced interferon gamma production by adult T cells in contrast to newborn T cells

Eur J Immunol. 2018 Apr;48(4):621-631. doi: 10.1002/eji.201747161. Epub 2018 Jan 18.

Abstract

Interferon gamma (IFN-γ) plays an important role in the antiviral immune response during respiratory syncytial virus (RSV) infections. Monocytes and T cells are recruited to the site of RSV infection, but it is unclear whether cell-cell interactions between monocytes and T cells regulate IFN-γ production. In this study, micro-array data identified the upregulation of sialic acid-binding immunoglobulin-type lectin 1 (Siglec-1) in human RSV-infected infants. In vitro, RSV increased expression of Siglec-1 on healthy newborn and adult monocytes. RSV-induced Siglec-1 on monocytes inhibited IFN-γ production by adult CD4+ T cells. In contrast, IFN-γ production by RSV in newborns was not affected by Siglec-1. The ligand for Siglec-1, CD43, is highly expressed on adult CD4+ T cells compared to newborns. Our data show that Siglec-1 reduces IFN-γ release by adult T cells possibly by binding to the highly expressed CD43. The Siglec-1-dependent inhibition of IFN-γ in adults and the low expression of CD43 on newborn T cells provides a better understanding of the immune response against RSV in early life and adulthood.

Keywords: CD43; Interferon gamma; Newborns; Respiratory syncytial virus; Siglec-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • CD4-Positive T-Lymphocytes / immunology*
  • Humans
  • Infant, Newborn
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / immunology
  • Leukosialin / metabolism
  • Monocytes / immunology*
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Infections / virology
  • Respiratory Syncytial Virus, Human / immunology*
  • Sialic Acid Binding Ig-like Lectin 1 / immunology*
  • Up-Regulation / immunology

Substances

  • IFNG protein, human
  • Leukosialin
  • SIGLEC1 protein, human
  • SPN protein, human
  • Sialic Acid Binding Ig-like Lectin 1
  • Interferon-gamma