LeBlanc Dana M, Barousse Melissa M, Fidel Paul L
Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Infect Immun. 2006 Jun;74(6):3213-21. doi: 10.1128/IAI.01824-05.
Vulvovaginal candidiasis (VVC) caused by the commensal organism Candida albicans remains a significant problem among women of childbearing age, with protection against and susceptibility to infection still poorly understood. While cell-mediated immunity by CD4+ Th1-type cells is protective against most forms of mucosal candidiasis, no protective role for adaptive immunity has been identified against VVC. This is postulated to be due to immunoregulation that prohibits a more profound Candida-specific CD4+ T-cell response against infection. The purpose of this study was to examine the role of dendritic cells (DCs) in the induction phase of the immune response as a means to understand the initiation of the immunoregulatory events. Immunostaining of DCs in sectioned murine lymph nodes draining the vagina revealed a profound cellular reorganization with DCs becoming concentrated in the T-cell zone throughout the course of experimental vaginal Candida infection consistent with cell-mediated immune responsiveness. However, analysis of draining lymph node DC subsets revealed a predominance of immunoregulation-associated CD11c+ B220+ plasmacytoid DCs (pDCs) under both uninfected and infected conditions. Staining of vaginal DCs showed the presence of both DEC-205+ and pDCs, with extension of dendrites into the vaginal lumen of infected mice in close contact with Candida. Flow cytometric analysis of draining lymph node DC costimulatory molecules and activation markers from infected mice indicated a lack of upregulation of major histocompatibility complex class II, CD80, CD86, and CD40 during infection, consistent with a tolerizing condition. Together, the results suggest that DCs are involved in the immunoregulatory events manifested during a vaginal Candida infection and potentially through the action of pDCs.
由共生生物体白色念珠菌引起的外阴阴道念珠菌病（VVC）仍是育龄女性面临的一个重大问题，人们对感染的防护和易感性仍知之甚少。虽然CD4 + Th1型细胞介导的细胞免疫可抵御大多数形式的黏膜念珠菌病，但尚未发现适应性免疫对VVC有保护作用。据推测，这是由于免疫调节抑制了针对感染的更强烈的念珠菌特异性CD4 + T细胞反应。本研究的目的是检查树突状细胞（DC）在免疫反应诱导阶段的作用，以此来了解免疫调节事件的起始过程。对引流阴道的小鼠淋巴结切片中的DC进行免疫染色显示，在实验性阴道念珠菌感染过程中，细胞发生了深刻的重组，DC集中在T细胞区，这与细胞介导的免疫反应性一致。然而，对引流淋巴结DC亚群的分析显示，在未感染和感染条件下，与免疫调节相关的CD11c + B220 +浆细胞样DC（pDC）均占主导。阴道DC的染色显示存在DEC - 205 +和pDC，感染小鼠的树突延伸到阴道腔内并与念珠菌紧密接触。对感染小鼠引流淋巴结DC共刺激分子和激活标志物的流式细胞术分析表明，感染期间主要组织相容性复合体II类、CD80、CD86和CD40均未上调，这与耐受状态一致。总之，结果表明DC参与了阴道念珠菌感染期间表现出的免疫调节事件，并且可能是通过pDC的作用。
