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

Abstract

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(-).

• Authors: Sara Tengvall, Ali M Harandi
• Journal: Journal of reproductive immunology (J Reprod Immunol) Vol. 78 Issue 1 Pg. 49-57 (Jun 2008) ISSN: 0165-0378 [Print] Ireland
• PMID: 17945349 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Viral
• CPG-oligonucleotide
• Herpesvirus Vaccines
• Immunoglobulin G
• Myd88 protein, mouse
• Myeloid Differentiation Factor 88
• Oligodeoxyribonucleotides
• Toll-Like Receptors
• Vaccines, Attenuated

Topics

• 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)