Importance of myeloid differentiation factor 88 in innate and acquired immune protection against genital herpes infection in mice.

• Toll-like receptors (TLRs) play an important role as pattern-recognition receptors to sense and respond to pathogens. Our laboratory and others have shown recently that activation of TLR/MyD88 signaling through vaginal administration of CpG oligodeoxynucleotides, either singly or in combination with recombinant glycoprotein from herpes simplex virus type 2 (HSV-2), confers immunity against genital herpes infection. In this study, we have investigated the importance of the myeloid differentiation factor 88 (MyD88), a critical adaptor protein shared by all TLRs, in innate and acquired immunity against genital HSV-2 infection in mice. We demonstrate that MyD88 is essential for innate immune resistance against HSV-2. Thus, MyD88 deficient (MyD88(-/-)) mice show more vaginal HSV-2 titers, more rapid disease progression and earlier death compared to C57Bl/6 mice following a vaginal challenge with high (9 x 10(4) PFU) or low (9 x 10(3) PFU) virus dose. In contrast, use of MyD88 appears dispensable for induction of HSV-specific serum IgG antibody as well as local and systemic cell-mediated immune responses elicited by vaginal immunization with live attenuated thymidine kinase-deficient HSV-2 (HSV-2 TK(-)). Importantly, and similar to immunized C57Bl/6 mice, immunized MyD88(-/-) mice were completely protected against subsequent vaginal challenge with a lethal dose of virulent strain of HSV-2. These results provide evidence that the adaptor protein MyD88 is important for innate early control of genital HSV-2 infection, and that use of MyD88 is not required for induction of acquired immunity following vaginal immunization with HSV-2 TK(-).

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

Antibodies

Viral

immunology

Female

Herpes Genitalis

immunology

Herpesvirus 2

Human

immunology

Herpesvirus Vaccines

pharmacology

Immunity

Cellular

drug effects

physiology

Immunity

Innate

drug effects

physiology

Immunization

Immunoglobulin G

immunology

Male

Mice

Mice

Knockout

Myeloid Differentiation Factor 88

genetics

immunology

Oligodeoxyribonucleotides

immunology

pharmacology

Signal Transduction

immunology

Toll-Like Receptors

immunology

Vaccines

Attenuated

pharmacology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)