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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Nyckelord

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

Natural

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

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)