title: NKT cell activation by local α-galactosylceramide administration decreases susceptibility to HSV-2 infection.
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.
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors: Marie Beck
authors: MB
authors: Iversen
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark; Aarhus Research Center for Innate Immunology, Aarhus University, Aarhus, Denmark.
authors: Simon Kok
authors: SK
authors: Jensen
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark; Aarhus Research Center for Innate Immunology, Aarhus University, Aarhus, Denmark.
authors: Anne Louise
authors: AL
authors: Hansen
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors: Henriette
authors: H
authors: Winther
authors: Neuroinflammation Unit, Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.
authors: Shohreh
authors: S
authors: Issazadeh-Navikas
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors: Line Sinnathamby
authors: LS
authors: Reinert
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark; Aarhus Research Center for Innate Immunology, Aarhus University, Aarhus, Denmark. Electronic address: holm@biomed.au.dk.
authors: Christian Kanstrup
authors: CK
authors: Holm
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005699:Galactosylceramides / Q000008:administration & dosage*; D006558:Herpes Genitalis / Q000276:immunology / Q000821:virology; D006561:Herpes Simplex / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000821:virology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D019562:Viral Load
chemical_list: D055610:Antigens, CD1d; D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D007371:Interferon-gamma
keywords: Herpes simplex virus 2; Innate immunity; Natural killer T cells; The murine intra-vaginal model; αGalCer