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α-半乳糖神经酰胺刺激的不变自然杀伤 T 细胞通过白念珠菌在小鼠阴道念珠菌病中发挥保护作用。

α-galactosylceramide-stimulated invariant natural killer T-cells play a protective role in murine vulvovaginal candidiasis by Candida albicans.

机构信息

Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan.

Department of Bacteriology, The Jikei University School of Medicine, Tokyo, Japan.

出版信息

PLoS One. 2021 Nov 16;16(11):e0259306. doi: 10.1371/journal.pone.0259306. eCollection 2021.

Abstract

BACKGROUND

Vulvovaginal candidiasis is a common superficial candidiasis; however, a host's immunological mechanism against vaginal Candida infection remains unknown.

OBJECTIVES

In this study, we aimed to elucidate the effect of iNKT cell activation on vulvovaginal candidiasis.

METHODS

Using a vulvovaginal candidiasis model with estrogenized mice, we evaluated the fungal burden and number of leukocyte infiltrations in the vaginal lavage of wild-type C57BL/6J mice after Candida albicans inoculation. One day before C. albicans inoculation, α-galactosylceramide (the α-GalCer group) or sterile phosphate-buffered saline (the sham group) was intraperitoneally injected into the mice. We also evaluated the level of antimicrobial peptide S100A8 in the vaginal lavage and analyzed the correlation between S100A8 concentration and the number of vaginal leukocyte infiltrations. Moreover, the number of uterine and vaginal immune cells were evaluated using flow cytometry.

RESULTS

The number of vaginal leukocyte infiltrations was significantly higher in the α-GalCer group than in the sham group 3 days after C. albicans inoculation. In addition, the fungal burden was significantly lower in the α-GalCer group than the sham group at 7 days after inoculation. In the analysis of S100A8 concentration of vaginal lavage, there were no significant differences between these two groups, although S100A8 concentration and the number of vaginal leukocyte infiltrations were positively correlated in the α-GalCer group. Moreover, the number of vaginal iNKT cells, NK cells and CD8+ T-cells was significantly higher in the α-GalCer group 3 days after inoculation.

CONCLUSIONS

α-GalCer-stimulated iNKT cells likely play a protective role against vulvovaginal candidiasis.

摘要

背景

外阴阴道假丝酵母菌病是一种常见的浅表假丝酵母菌病;然而,宿主对阴道念珠菌感染的免疫机制尚不清楚。

目的

本研究旨在阐明自然杀伤 T(NKT)细胞的激活对外阴阴道假丝酵母菌病的影响。

方法

采用雌激素化小鼠的外阴阴道假丝酵母菌病模型,评估阴道灌洗液中白色念珠菌接种后野生型 C57BL/6J 小鼠的真菌负荷和白细胞浸润数量。在接种白色念珠菌前 1 天,将 α-半乳糖神经酰胺(α-GalCer 组)或无菌磷酸盐缓冲液(假手术组)腹腔内注射到小鼠体内。我们还评估了阴道灌洗液中抗菌肽 S100A8 的水平,并分析了 S100A8 浓度与阴道白细胞浸润数量之间的相关性。此外,还使用流式细胞术评估了子宫和阴道免疫细胞的数量。

结果

白色念珠菌接种后 3 天,α-GalCer 组阴道白细胞浸润数量明显高于假手术组。此外,接种后 7 天,α-GalCer 组的真菌负荷明显低于假手术组。在阴道灌洗液中 S100A8 浓度分析中,两组之间没有显著差异,尽管 α-GalCer 组中 S100A8 浓度与阴道白细胞浸润数量呈正相关。此外,接种后 3 天,α-GalCer 组阴道内 NKT 细胞、NK 细胞和 CD8+T 细胞的数量明显增加。

结论

α-GalCer 刺激的 NKT 细胞可能在外阴阴道假丝酵母菌病中发挥保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2701/8594805/c86d78a57791/pone.0259306.g001.jpg

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