Phenotypic and functional characterization of vaginal dendritic cells in a rat model of Candida albicans vaginitis
Phenotypic and functional characterization of vaginal dendritic cells in a rat model of Candida albicans vaginitis
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DOI：
10.1128/iai.01714-05
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发表时间：
2006-07-01
影响因子：
3.1
通讯作者：
Santoni, Giorgio
中科院分区：
文献类型：
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作者：
De Bernardis, Flavia;Lucciarini, Roberta;Santoni, Giorgio
本研究分析了阴道树突状细胞（VDCs）的表型，其抗原呈递和T细胞细胞因子分泌的激活，以及它们在念珠菌性阴道炎大鼠模型中的保护作用。组织学观察表明，在第三轮感染时，白色念珠菌感染大鼠的粘膜上皮中OX 62（+）VDCs显着积聚。我们在未感染和念珠菌感染的大鼠中鉴定了两个OX 62（+）VDCs亚群，其CD 4分子表达不同。VDC的OX 62（+）CD 4（+）亚群显示淋巴样细胞形态并表达T细胞抗原CD 5，而OX 62（+）CD 4（-）VDC亚群显示髓样形态并为CD 5阴性。念珠菌感染导致VDC成熟，在念珠菌感染后2周和6周，CD 4（+）和CD 4- VDC亚群上的CD 80和CD 134 L表达增强。CD 5（-）CD 4（-）CD 86（-）CD 80（-）CD 134 L（+）VDC从感染的大鼠自发释放大量的白细胞介素-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OX 62（+）VDC在体外对葡萄球菌肠毒素B刺激的应答中引发幼稚CD 4（+）T细胞增殖和细胞因子（包括γ干扰素、IL-2、IL-6和IL-10）的释放。从感染大鼠连续转移高度纯化的OX 62（+）VDCs诱导真菌清除显著加速，与接受初始VDCs的大鼠相比，表明VDCs在抗念珠菌粘膜免疫中的保护作用。最后，VDC介导的保护作用与其快速迁移至阴道粘膜和淋巴结的能力相关，如通过5（和6-）-羧基荧光素二乙酸琥珀酰亚胺酯标记的OX 62（+）VDC的过继转移所评估的。
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 naive 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.