Cheng Kar On, Montaño Dolly E, Zelante Teresa, Dietschmann Axel, Gresnigt Mark S
Junior Research Group Adaptive Pathogenicity Strategies, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute (Leibniz-HKI), Beutenbergstraße 11a, Jena, 07749, Germany.
Department of Medicine and Surgery, University of Perugia, Piazza Lucio Severi 1, Perugia, 06132, Italy.
Oxf Open Immunol. 2024 Aug 17;5(1):iqae010. doi: 10.1093/oxfimm/iqae010. eCollection 2024.
Protective immunity to opportunistic fungal infections consists of tightly regulated innate and adaptive immune responses that clear the infection. Immune responses to infections of the vaginal mucosa by species are, however, an exception. In the case of vulvovaginal candidiasis (VVC), the inflammatory response is associated with symptomatic disease, rather than that it results in pathogen clearance. As such VVC can be considered an inflammatory disease, which is a significant public health problem due to its predominance as a female-specific fungal infection. Particularly, women with recurrent VVC (RVVC) suffer from a significant negative impact on their quality of life and mental health. Knowledge of the inflammatory pathogenesis of (R)VVC may guide more effective diagnostic and therapeutic options to improve the quality of life of women with (R)VVC. Here, we review the immunopathogenesis of (R)VVC describing several elements that induce an inflammatory arson, starting with the activation threshold established by vaginal epithelial cells that prevent unnecessary ignition of inflammatory responses, epithelial and inflammasome-dependent immune responses. These inflammatory responses will drive neutrophil recruitment and dysfunctional neutrophil-mediated inflammation. We also review the, sometimes controversial, findings on the involvement of adaptive and systemic responses. Finally, we provide future perspectives on the potential of some unexplored cytokine axes and discuss whether VVC needs to be subdivided into subgroups to improve diagnosis and treatment.
对机会性真菌感染的保护性免疫由清除感染的严格调控的固有免疫和适应性免疫反应组成。然而，阴道黏膜对真菌感染的免疫反应却是个例外。就外阴阴道念珠菌病（VVC）而言，炎症反应与症状性疾病相关，而非导致病原体清除。因此，VVC可被视为一种炎症性疾病，由于其作为女性特有的真菌感染占主导地位，它是一个重大的公共卫生问题。特别是，复发性VVC（RVVC）患者的生活质量和心理健康受到严重负面影响。了解（复发性）VVC的炎症发病机制可能会指导更有效的诊断和治疗选择，以提高（复发性）VVC患者的生活质量。在此，我们综述（复发性）VVC的免疫发病机制，描述引发炎症的几个因素，首先是阴道上皮细胞建立的激活阈值，该阈值可防止炎症反应的不必要激发、上皮细胞和炎性小体依赖性免疫反应。这些炎症反应将促使中性粒细胞募集和功能失调的中性粒细胞介导的炎症。我们还综述了关于适应性和全身反应参与情况的一些有时存在争议的发现。最后，我们提供了关于一些未探索的细胞因子轴潜力的未来展望，并讨论了VVC是否需要细分为亚组以改善诊断和治疗。
