De Bernardis Flavia, Lucciarini Roberta, Boccanera Maria, Amantini Consuelo, Arancia Silvia, Morrone Stefania, Mosca Michela, Cassone Antonio, Santoni Giorgio
Department of Experimental Medicine and Public Health, University of Camerino, via Scalzino 3, 62032 Camerino (MC), Italy.
Infect Immun. 2006 Jul;74(7):4282-94. doi: 10.1128/IAI.01714-05.
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.
本研究分析了阴道树突状细胞（VDC）的表型、其抗原呈递及对T细胞细胞因子分泌的激活作用，以及它们在念珠菌性阴道炎大鼠模型中的保护作用。组织学观察显示，在第三轮感染时，白色念珠菌感染大鼠的黏膜上皮中OX62(+) VDC显著积聚。我们在未感染和念珠菌感染的大鼠中均鉴定出OX62(+) VDC的两个亚群，它们在CD4分子表达上存在差异。VDC的OX62(+) CD4(+)亚群呈现淋巴细胞样形态并表达T细胞抗原CD5，而OX62(+) CD4(-) VDC亚群呈现髓样形态且CD5阴性。念珠菌感染导致VDC成熟，在念珠菌感染后2周和6周，CD4(+)和CD4(-) VDC亚群上的CD80和CD134L表达均增强。来自感染而非未感染大鼠的CD5(-) CD4(-) CD86(-) CD80(-) CD134L(+) VDC自发释放大量白细胞介素-12（IL-12）和肿瘤坏死因子α，而所有VDC亚群释放的IL-10和IL-2细胞因子水平相当。此外，来自感染大鼠的OX62(+) VDC在体外经葡萄球菌肠毒素B刺激后，可启动幼稚CD4(+) T细胞增殖并释放包括γ干扰素、IL-2、IL-6和IL-10在内的细胞因子。与接受未处理VDC的大鼠相比，经感染大鼠高度纯化的OX62(+) VDC的过继转移诱导真菌清除显著加速，表明VDC在抗念珠菌黏膜免疫中具有保护作用。最后，通过用5（和6-）-羧基荧光素二乙酸琥珀酰亚胺酯标记的OX62(+) VDC的过继转移评估，VDC介导的保护作用与其快速迁移至阴道黏膜和淋巴结的能力相关。
