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Infection and Immunity, July 2006, p. 4282-4294, Vol. 74, No. 7
0019-9567/06/$08.00+0 doi:10.1128/IAI.01714-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Department of Infectious Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy,1 Department of Experimental Medicine and Public Health, University of Camerino, Camerino, Italy,2 Department of Experimental Medicine and Pathology, University of Rome La Sapienza, Rome, Italy3
Received 20 October 2005/ Returned for modification 10 November 2005/ Accepted 12 April 2006
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.
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