Intravaginal live Candida challenge in humans leads to new hypotheses for the immunopathogenesis of vulvovaginal candidiasis

Intravaginal live Candida challenge in humans leads to new hypotheses for the immunopathogenesis of vulvovaginal candidiasis
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DOI:
10.1128/iai.72.5.2939-2946.2004
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发表时间:
2004-05-01
影响因子:
3.1
通讯作者:
Dunlap, K
Dunlap, K
中科院分区:
医学2区
文献类型:
--
作者:
Fidel, PL;Barousse, M;Dunlap, K

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急性和复发性外阴阴道念珠菌病(WC)仍然是育龄妇女的一个重大问题。虽然对患有复发性 WC (RVVC) 的女性和动物模型的临床研究提供了关于适应性免疫的有限保护作用的重要数据,但关于与感染易感性相关的保护机制或因素的信息仍然很少。在本研究中,健康成年女性的阴道内活念珠菌攻击显示出对症状性WC的易感性不同,其中19名没有WC史的女性中有3人(15%)获得了症状感染,而11名很少有WC史的女性中有6人(55%)获得了症状感染。此外,这些研究表明,针对感染的保护是非炎症性的,而有症状的感染则与多形核中性粒细胞(PMN)的阴道浸润和阴道真菌负荷高有关。因此,有症状感染的存在似乎更依赖于宿主因素而不是生物体的特性。最后,有症状感染女性(而非无症状定植女性)的阴道灌洗液促进了中性粒细胞的趋化性。这些结果表明,RVVC/VVC 不是由异常的适应性免疫反应引起的,定义感染的症状似乎是由于 PMN 的攻击性先天反应所致。
Acute and recurrent vulvovaginal candidiasis (WC) remains a significant problem in women of childbearing age. While clinical studies of women with recurrent WC (RVVC) and animal models have provided important data about a limited protective role of adaptive immunity, there remains a paucity of information on the protective mechanisms or factors associated with susceptibility to infection. In the present study, an intravaginal live Candida challenge in healthy adult women showed a differential susceptibility to symptomatic WC, where 3 (15%) of 19 women with no history of WC acquired a symptomatic infection compared to 6 (55%) of 11 women with an infrequent history of WC. Furthermore, these studies revealed that protection against infection is noninflammatory while symptomatic infection correlates with a vaginal infiltration of polymorphonuclear neutrophils (PMNs) and a high vaginal fungal burden. Thus, the presence of symptomatic infection appears more dependent on host factors than on properties of the organism. Finally, vaginal lavage fluid from women with a symptomatic infection, but not those asymptomatically colonized, promoted the chemotaxis of PMNs. These results suggest that rather than RVVC/VVC being caused by an aberrant adaptive immune response, symptoms that define infection appear to be due to an aggressive innate response by PMNs.