Neurokinin 1 receptor signaling affects the local innate immune defense against genital herpes virus infection.

Abstract

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.

• Authors: Alexandra Svensson, Joanna Kaim, Carina Mallard, Annika Olsson, Ernst Brodin, Tomas Hökfelt, Kristina Eriksson
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 175 Issue 10 Pg. 6802-11 (Nov 15 2005) ISSN: 0022-1767 [Print] United States
• PMID: 16272337 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Herpes Simplex Virus Vaccines
• Receptors, Neurokinin-1
• Vaccines, Attenuated
• Substance P

Topics

• Animals
• Central Nervous System (pathology, virology)
• Female
• Herpes Genitalis (immunology, metabolism, prevention & control, virology)
• Herpes Simplex Virus Vaccines (pharmacology)
• Herpesvirus 2, Human (drug effects, immunology, physiology)
• Immunity, Innate
• In Vitro Techniques
• Killer Cells, Natural (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Receptors, Neurokinin-1 (deficiency, genetics, immunology)
• Signal Transduction
• Substance P (metabolism, pharmacology)
• Vaccines, Attenuated (pharmacology)
• Vagina (immunology, metabolism, virology)
• Virus Replication (drug effects)