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

TY - JOUR

T1 - NKT cell activation by local α-galactosylceramide administration decreases susceptibility to HSV-2 infection

AU - Iversen, Marie Beck

AU - Jensen, Simon Kok

AU - Hansen, Anne Louise

AU - Winther, Henriette

AU - Issazadeh-Navikas, Shohreh

AU - Reinert, Line Sinnathamby

AU - Holm, Christian Kanstrup

N1 - Copyright © 2014 Elsevier GmbH. All rights reserved.

PY - 2015/6/1

Y1 - 2015/6/1

N2 - 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.

AB - 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.

U2 - 10.1016/j.imbio.2014.12.019

DO - 10.1016/j.imbio.2014.12.019

M3 - Journal article

C2 - 25648689

SN - 0171-2985

JO - Immunobiology

JF - Immunobiology

ER -