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Updated: Apr 17, 2026
Isolation of Lymphocytes from Mouse Genital Tract Mucosa
Published on: September 3, 2012
NKT cell activation by local α-galactosylceramide administration decreases susceptibility to HSV-2 infection
Marie Beck Iversen1, Simon Kok Jensen2, Anne Louise Hansen2
1Department of Biomedicine, Aarhus University, Aarhus, Denmark.
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.
Insights
Pre-treating mice with αGalCer, a marine sponge lipid, activated Natural Killer T (NKT) cells. This activation provided significant immune protection against vaginal herpes simplex virus type 2 (HSV-2) infection.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- Natural Killer T (NKT) cells are crucial for innate immunity against viral infections.
- NKT cell activation relies on the CD1d molecule presenting bioactive lipids.
- α-Galactosylceramide (αGalCer), a marine sponge lipid, specifically activates human and murine NKT cells.
Purpose of the Study:
- To investigate the protective potential of αGalCer pre-treatment against vaginal HSV-2 infection.
- To evaluate the impact of αGalCer on immune cell populations and cytokine levels in the vaginal environment.
Main Methods:
- C57BL/6 wild-type mice were pre-treated locally with αGalCer.
- Mice were subsequently infected intra-vaginally with HSV-2.
- Disease scores, mortality, viral load, immune cell infiltration (CD45, NK1.1), and IFN-γ levels were assessed.
Main Results:
- αGalCer pre-treatment significantly reduced disease severity, mortality, and vaginal viral load post-HSV-2 infection.
- Increased infiltration of CD45 and NK1.1 positive immune cells was observed in vaginal tissue.
- Elevated levels of Interferon-gamma (IFN-γ) were detected in vaginal tissue and fluids 24 hours after αGalCer administration.
Conclusions:
- αGalCer pre-treatment confers a protective immune response against vaginal HSV-2 infection.
- The protective effect is mediated by the activation of NKT cells, leading to enhanced innate immunity.
- αGalCer represents a potential therapeutic strategy for managing viral infections.
