NKT cell activation by local α-galactosylceramide administration decreases susceptibility to HSV-2 infection

Immunobiology. 2015 Jun;220(6):762-8. doi: 10.1016/j.imbio.2014.12.019. Epub 2015 Jan 21.

Abstract

NKT cells are a subgroup of T cells, which express a restricted TCR repertoire and are critical for the innate immune responses to viral infections. Activation of NKT cells depends on the major histocompatibility complex-related molecule CD1d, which presents bioactive lipids to NKT cells. The marine sponge derived lipid αGalCer has recently been demonstrated as a specific agonist for activation of human and murine NKT cells. In the present study we investigated the applicability of αGalCer pre-treatment for immune protection against intra-vaginal HSV-2 infection. We found that C57BL/6 WT mice that received local pre-treatment with αGalCer prior to intra-vaginal HSV-2 infection had a lower mean disease score, mortality and viral load in the vagina following infection, compared to mice that did not receive αGalCer pre-treatment. Further, we found increased numbers of CD45 and NK1.1 positive cells in vaginal tissue and elevated levels of IFN-γ in the vaginal tissue and in vaginal fluids 24h after αGalCer pre-treatment. Collectively our data demonstrate a protective effect of αGalCer induced activation of NKT cells in the innate immune protection against viral infection.

Keywords: Herpes simplex virus 2; Innate immunity; Natural killer T cells; The murine intra-vaginal model; αGalCer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD1d / genetics
  • Disease Models, Animal
  • Disease Susceptibility*
  • Galactosylceramides / administration & dosage*
  • Herpes Genitalis / immunology
  • Herpes Genitalis / virology
  • Herpes Simplex / immunology*
  • Herpes Simplex / mortality
  • Herpes Simplex / pathology
  • Herpes Simplex / virology*
  • Herpesvirus 2, Human / immunology*
  • Humans
  • Interferon-gamma / biosynthesis
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Knockout
  • Natural Killer T-Cells / immunology*
  • Natural Killer T-Cells / metabolism
  • Viral Load

Substances

  • Antigens, CD1d
  • Galactosylceramides
  • alpha-galactosylceramide
  • Interferon-gamma