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Vaginal Submucosal Dendritic Cells, but Not Langerhans Cells, Induce Protective Th1 Responses to Herpes Simplex Virus-2

Herpes simplex virus (HSV) type 2 infection occurs primarily at the genital mucosal surfaces and is a leading cause of ulcerative lesions. Despite the availability of animal models for HSV-2 infection, little is known regarding the mechanism of immune induction within the vaginal mucosa. Here, we ex...

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Autores principales: Zhao, Xinyan, Deak, Eszter, Soderberg, Kelly, Linehan, Melissa, Spezzano, David, Zhu, Jia, Knipe, David M., Iwasaki, Akiko
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193810/
https://www.ncbi.nlm.nih.gov/pubmed/12538655
http://dx.doi.org/10.1084/jem.20021109
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author Zhao, Xinyan
Deak, Eszter
Soderberg, Kelly
Linehan, Melissa
Spezzano, David
Zhu, Jia
Knipe, David M.
Iwasaki, Akiko
author_facet Zhao, Xinyan
Deak, Eszter
Soderberg, Kelly
Linehan, Melissa
Spezzano, David
Zhu, Jia
Knipe, David M.
Iwasaki, Akiko
author_sort Zhao, Xinyan
collection PubMed
description Herpes simplex virus (HSV) type 2 infection occurs primarily at the genital mucosal surfaces and is a leading cause of ulcerative lesions. Despite the availability of animal models for HSV-2 infection, little is known regarding the mechanism of immune induction within the vaginal mucosa. Here, we examined the cell types responsible for the initiation of protective Th1 immunity to HSV-2. Intravaginal inoculation of HSV-2 led to a rapid recruitment of submucosal dendritic cells (DCs) to the infected epithelium. Subsequently, CD11c(+) DCs harboring viral peptides in the context of MHC class II molecules emerged in the draining lymph nodes and were found to be responsible for the stimulation of IFNγ secretion from HSV-specific CD4(+) T cells. Other antigen-presenting cells including B cells and macrophages did not present viral peptides to T cells in the draining lymph nodes. Next, we assessed the relative contribution to immune generation by the Langerhans cells in the vaginal epithelium, the submucosal CD11b(+) DCs, and the CD8α(+) lymph node DCs. Analysis of these DC populations from the draining lymph nodes revealed that only the CD11b(+) submucosal DCs, but not Langerhans cell–derived or CD8α(+) DCs, presented viral antigens to CD4(+) T cells and induced IFNγ secretion. These results demonstrate a previously unanticipated role for submucosal DCs in the generation of protective Th1 immune responses to HSV-2 in the vaginal mucosa, and suggest their importance in immunity to other sexually transmitted diseases.
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spelling pubmed-21938102008-04-11 Vaginal Submucosal Dendritic Cells, but Not Langerhans Cells, Induce Protective Th1 Responses to Herpes Simplex Virus-2 Zhao, Xinyan Deak, Eszter Soderberg, Kelly Linehan, Melissa Spezzano, David Zhu, Jia Knipe, David M. Iwasaki, Akiko J Exp Med Article Herpes simplex virus (HSV) type 2 infection occurs primarily at the genital mucosal surfaces and is a leading cause of ulcerative lesions. Despite the availability of animal models for HSV-2 infection, little is known regarding the mechanism of immune induction within the vaginal mucosa. Here, we examined the cell types responsible for the initiation of protective Th1 immunity to HSV-2. Intravaginal inoculation of HSV-2 led to a rapid recruitment of submucosal dendritic cells (DCs) to the infected epithelium. Subsequently, CD11c(+) DCs harboring viral peptides in the context of MHC class II molecules emerged in the draining lymph nodes and were found to be responsible for the stimulation of IFNγ secretion from HSV-specific CD4(+) T cells. Other antigen-presenting cells including B cells and macrophages did not present viral peptides to T cells in the draining lymph nodes. Next, we assessed the relative contribution to immune generation by the Langerhans cells in the vaginal epithelium, the submucosal CD11b(+) DCs, and the CD8α(+) lymph node DCs. Analysis of these DC populations from the draining lymph nodes revealed that only the CD11b(+) submucosal DCs, but not Langerhans cell–derived or CD8α(+) DCs, presented viral antigens to CD4(+) T cells and induced IFNγ secretion. These results demonstrate a previously unanticipated role for submucosal DCs in the generation of protective Th1 immune responses to HSV-2 in the vaginal mucosa, and suggest their importance in immunity to other sexually transmitted diseases. The Rockefeller University Press 2003-01-20 /pmc/articles/PMC2193810/ /pubmed/12538655 http://dx.doi.org/10.1084/jem.20021109 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Zhao, Xinyan
Deak, Eszter
Soderberg, Kelly
Linehan, Melissa
Spezzano, David
Zhu, Jia
Knipe, David M.
Iwasaki, Akiko
Vaginal Submucosal Dendritic Cells, but Not Langerhans Cells, Induce Protective Th1 Responses to Herpes Simplex Virus-2
title Vaginal Submucosal Dendritic Cells, but Not Langerhans Cells, Induce Protective Th1 Responses to Herpes Simplex Virus-2
title_full Vaginal Submucosal Dendritic Cells, but Not Langerhans Cells, Induce Protective Th1 Responses to Herpes Simplex Virus-2
title_fullStr Vaginal Submucosal Dendritic Cells, but Not Langerhans Cells, Induce Protective Th1 Responses to Herpes Simplex Virus-2
title_full_unstemmed Vaginal Submucosal Dendritic Cells, but Not Langerhans Cells, Induce Protective Th1 Responses to Herpes Simplex Virus-2
title_short Vaginal Submucosal Dendritic Cells, but Not Langerhans Cells, Induce Protective Th1 Responses to Herpes Simplex Virus-2
title_sort vaginal submucosal dendritic cells, but not langerhans cells, induce protective th1 responses to herpes simplex virus-2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193810/
https://www.ncbi.nlm.nih.gov/pubmed/12538655
http://dx.doi.org/10.1084/jem.20021109
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