Phenotypic and functional characterization of vaginal dendritic cells in a rat model of Candida albicans vaginitis.
This study analyzes the phenotype of vaginal dendritic cells (VDCs), their antigenic presentation and activation of T-cell cytokine secretion, and their protective role in a rat model of Candida vaginitis. Histological observation demonstrated a significant accumulation of OX62(+) VDCs in the mucosal epithelium of Candida albicans-infected rats at the third round of infection. We identified two subsets of OX62(+) VDCs differing in the expression of CD4 molecule in both noninfected and Candida-infected rats. The OX62(+) CD4(+) subset of VDCs displayed a lymphoid cell-like morphology and expressed the T-cell antigen CD5, whereas the OX62(+) CD4(-) VDC subset exhibited a myeloid morphology and was CD5 negative. Candida infection resulted in VDC maturation with enhanced expression of CD80 and CD134L on both CD4(+) and CD4(-) VDC subsets at 2 and 6 weeks after Candida infection. CD5(-) CD4(-) CD86(-) CD80(-) CD134L(+) VDCs from infected, but not noninfected, rats spontaneously released large amounts of interleukin-12 (IL-12) and tumor necrosis factor alpha, whereas all VDC subsets released comparable levels of IL-10 and IL-2 cytokines. Furthermore, OX62(+) VDCs from infected rats primed naïve CD4(+) T-cell proliferation and release of cytokines, including gamma interferon, IL-2, IL-6, and IL-10, in response to staphylococcal enterotoxin B stimulation in vitro. Adoptive transfer of highly purified OX62(+) VDCs from infected rats induced a significant acceleration of fungal clearance compared with that in rats receiving naive VDCs, suggesting a protective role of VDCs in the anti-Candida mucosal immunity. Finally, VDC-mediated protection was associated with their ability to rapidly migrate to the vaginal mucosa and lymph nodes, as assessed by adoptive transfer of OX62(+) VDCs labeled with 5 (and 6-)-carboxyfluorescein diacetate succinimidyl ester.
De Bernardis
Flavia
F
Department of Experimental Medicine and Public Health, University of Camerino, via Scalzino 3, 62032 Camerino (MC), Italy.
Lucciarini
Roberta
R
Boccanera
Maria
M
Amantini
Consuelo
C
Arancia
Silvia
S
Morrone
Stefania
S
Mosca
Michela
M
Cassone
Antonio
A
Santoni
Giorgio
G
D019264:Adoptive Transfer; D000818:Animals; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D005260:Female; D018928:Immunity, Mucosal; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014621:Vagina / Q000276:immunology / Q000473:pathology; D014627:Vaginitis / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control