益生菌乳酸杆菌属在阴道上皮细胞定植过程中调节免疫反应。

Probiotic Lactobacillus species modulate immune responses during vaginal epithelial cell colonization.

作者信息

Valentine Marisa, Rosati Diletta, Dietschmann Axel, Schille Tim B, Netea Mihai G, Hube Bernhard, Gresnigt Mark S

机构信息

Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute (HKI), Jena, Germany.

Department of Internal Medicine and Radboud Centre for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.

出版信息

J Infect Dis. 2025 May 15. doi: 10.1093/infdis/jiaf221.

Abstract

BACKGROUND

Vulvovaginal candidiasis (VVC), mainly caused by Candida albicans, affects approximately 75% of women at least once during their lifetime. VVC is characterized by fungal colonization, which leads to inappropriate local hyperinflammation and symptoms. Although the trigger of C. albicans pathogenicity is often unknown, antibiotic use and vaginal dysbiosis are associated with increased susceptibility to VVC. A healthy vaginal microbiota is normally dominated by Lactobacillus species, which are believed to keep C. albicans infections at bay. Probiotic lactobacilli are, therefore, explored to treat symptomatic VVC episodes. However, the influence of probiotic lactobacilli on immune responses in the context of VVC remains underexplored.

METHODS

We investigated how probiotic lactobacilli influence vaginal epithelial and downstream inflammatory responses during C. albicans infection, using in vitro vaginal epithelial infection models and stimulating primary human immune cells with supernatants from these vaginal epithelial cells.

RESULTS

Our study shows that although most of the tested probiotic lactobacilli reduced C. albicans-induced vaginal epithelial cell damage, some species, particularly Limosilactobacillus fermentum and Lacticaseibacillus paracasei, elicited proinflammatory responses even in the absence of C. albicans. Probiotic lactobacilli also differentially modulated the C. albicans killing efficiency and production of reactive oxygen species by neutrophils.

CONCLUSIONS

Overall, vaginal epithelial and downstream immune responses during co-cultivation with C. albicans and probiotic lactobacilli were mostly driven by specific bacterial species and their interactions with the vaginal epithelium. Therefore, the induction of "controlled" inflammation by probiotic lactobacilli may be beneficial to improve neutrophil function, however, whether this alleviates immunopathology warrants further investigation.

摘要

背景

外阴阴道念珠菌病(VVC)主要由白色念珠菌引起,约75%的女性在其一生中至少会感染一次。VVC的特征是真菌定植,这会导致局部不适当的过度炎症和症状。尽管白色念珠菌致病性的触发因素通常不明,但抗生素的使用和阴道生态失调与VVC易感性增加有关。健康的阴道微生物群通常以乳酸杆菌为主,据信其可抑制白色念珠菌感染。因此,人们探索使用益生菌乳酸杆菌来治疗有症状的VVC发作。然而,在VVC背景下益生菌乳酸杆菌对免疫反应的影响仍未得到充分研究。

方法

我们使用体外阴道上皮感染模型,并使用这些阴道上皮细胞的上清液刺激原代人免疫细胞,研究了益生菌乳酸杆菌在白色念珠菌感染期间如何影响阴道上皮及下游炎症反应。

结果

我们的研究表明,尽管大多数测试的益生菌乳酸杆菌减少了白色念珠菌诱导的阴道上皮细胞损伤,但某些菌株,特别是发酵乳杆菌和副干酪乳杆菌,即使在没有白色念珠菌的情况下也会引发促炎反应。益生菌乳酸杆菌还对中性粒细胞杀死白色念珠菌的效率和活性氧的产生进行了不同程度的调节。

结论

总体而言,与白色念珠菌和益生菌乳酸杆菌共培养期间的阴道上皮及下游免疫反应大多由特定细菌种类及其与阴道上皮的相互作用驱动。因此,益生菌乳酸杆菌诱导的“可控”炎症可能有利于改善中性粒细胞功能,然而,这是否能减轻免疫病理学仍有待进一步研究。

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