Neurokinin 1 Receptor Signaling Affects the Local Innate Immune Defense against Genital Herpes Virus Infection
| Autor: | Ernst Brodin, Annika Olsson, Carina Mallard, Tomas Hökfelt, Alexandra Svensson, Kristina Eriksson, Joanna Kaim |
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| Rok vydání: | 2005 |
| Předmět: |
Central Nervous System
Herpesvirus 2 Human viruses T cell Immunology Substance P In Vitro Techniques Biology Vaccines Attenuated Virus Replication Virus Mice chemistry.chemical_compound Immune system Immunity medicine Animals Immunology and Allergy Receptor Mice Knockout Herpes Genitalis Innate immune system Herpes Simplex Virus Vaccines Receptors Neurokinin-1 Immunity Innate Killer Cells Natural Mice Inbred C57BL medicine.anatomical_structure chemistry Viral replication Vagina Female Signal Transduction |
| Zdroj: | The Journal of Immunology. 175:6802-6811 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.175.10.6802 |
| Popis: | We show that genital infection with neurotropic HSV type 2 (HSV-2) induced a significant increase of the neuropeptide substance P (SP) within the genital tract of mice. SP was shown to weakly interfere with the HSV-2 replication. Furthermore, lack of SP signaling through the use of mice deficient in the SP receptor, neurokinin 1 receptor (NK1R), revealed an important role for SP in the innate defense against HSV-2. NK1R-deficient mice had significantly enhanced levels of HSV-2 in the genital tract and in the CNS following infection and a significantly accelerated disease progression, which was associated with an impaired NK cell activity locally in the vagina. Lack of NK1R signaling did, however, not impair the animals’ ability to mount a protective immune response to HSV-2 following vaccination with an attenuated virus. Both NK1R+/+ and NK1R−/− mice developed strong HSV-2-specific Th1 T cell responses following vaccination. No genital viral replication was observed in either vaccinated NK1R-deficient or NK1R+/+ control animals following a genital HSV-2 challenge, and all of these animals survived without any symptoms of disease. In conclusion, the present results indicate that SP and NK1R signaling contributes to the innate resistance against HSV-2 infection in mice. |
| Databáze: | OpenAIRE |
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