title: Vaginal submucosal dendritic cells, but not Langerhans cells, induce protective Th1 responses to herpes simplex virus-2.
abstract: 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 IFNgamma 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 CD8alpha(+) 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 CD8alpha(+) DCs, presented viral antigens to CD4(+) T cells and induced IFNgamma 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.
authors.affiliation: Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College Street, New Haven, CT 06520, USA.
authors.forename: Xinyan
authors.initials: X
authors.lastname: Zhao
authors.forename: Eszter
authors.initials: E
authors.lastname: Deak
authors.forename: Kelly
authors.initials: K
authors.lastname: Soderberg
authors.forename: Melissa
authors.initials: M
authors.lastname: Linehan
authors.forename: David
authors.initials: D
authors.lastname: Spezzano
authors.forename: Jia
authors.initials: J
authors.lastname: Zhu
authors.forename: David M
authors.initials: DM
authors.lastname: Knipe
authors.forename: Akiko
authors.initials: A
authors.lastname: Iwasaki
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D004971:Estrus; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D007371:Interferon-gamma / Q000096:biosynthesis; D007801:Langerhans Cells / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000276:immunology / Q000821:virology; D018417:Th1 Cells / Q000276:immunology*; D014621:Vagina / Q000276:immunology* / Q000821:virology; D014764:Viral Proteins / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D014764:Viral Proteins; D007371:Interferon-gamma