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Importance of myeloid differentiation factor 88 in innate and acquired immune protection against genital herpes infection in mice.
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- Tengvall, Sara, 1977 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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- Harandi, Ali M, 1968 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
- (creator_code:org_t)
- Elsevier BV, 2008
- 2008
- English.
- In: Journal of reproductive immunology. - : Elsevier BV. - 0165-0378. ; 78:1, s. 49-57
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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(-).
Subject headings
- 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)
Keyword
- 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
Publication and Content Type
- ref (subject category)
- art (subject category)
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