皮质类固醇通过损害17型免疫而不诱导干扰素-γ病来驱动口腔念珠菌病。

文献信息

中文摘要

口腔念珠菌病可由遗传性免疫缺陷或医源性免疫抑制引起，最常见的原因是皮质类固醇治疗。尽管醋酸可的松小鼠模型被广泛用于研究皮质类固醇相关的口腔念珠菌病，但其易感性的潜在机制仍不清楚。在这里，我们表明皮质类固醇诱导的口腔念珠菌病易感性主要由17型免疫受损驱动。相反，干扰素-γ病，另一种已知促进口腔念珠菌病的免疫状态，在可的松模型中不促进疾病。此外，在17型信号缺陷的情况下，干扰素-γ病不是口腔念珠菌病易感性所必需的。总之，这些发现表明17型免疫缺陷和干扰素-γ病代表口腔念珠菌病的独立、非重叠途径，并确立受损的17型免疫是皮质类固醇诱导疾病的主要机制。重要性：白色念珠菌通常无害地生活在口腔中，但过度生长可导致口腔念珠菌病，这是一种疼痛的感染，可干扰进食和吞咽。口腔念珠菌病最常见的原因之一是皮质类固醇治疗，这些药物广泛用于控制自身免疫性和过敏性疾病。尽管已知皮质类固醇会削弱免疫防御，但尚不清楚哪些免疫途径受损以促进对这种感染的易感性。我们表明，皮质类固醇通过抑制一种特定的保护性免疫反应，即17型免疫，而不是通过触发由干扰素-γ驱动的过度炎症反应来促进口腔念珠菌病。我们进一步证明，这两种免疫改变——17型免疫的丧失和干扰素-γ驱动的炎症——通过独立机制导致口腔念珠菌病。这些发现阐明了皮质类固醇如何使患者易患口腔念珠菌病，并完善了我们对通常保护口腔黏膜的免疫途径的理解。

英文摘要

Oral candidiasis arises from either genetic immune defects or iatrogenic immune suppression, most commonly due to corticosteroid therapy. Although the cortisone acetate mouse model is widely used to study corticosteroid-associated oral candidiasis, the underlying mechanisms of susceptibility remain poorly defined. Here, we show that corticosteroid-induced susceptibility to oral candidiasis is driven primarily by impairment of type-17 immunity. In contrast, interferon-gammopathy, another immune state known to promote oral candidiasis, does not contribute to disease in the cortisone model. Moreover, interferon-gammopathy is not required for susceptibility to oral candidiasis in the setting of type-17 signaling deficiency. Taken together, these findings demonstrate that type-17 immune deficiency and interferon-gammopathy represent independent, non-overlapping pathways to oral candidiasis and establish impaired type-17 immunity as the dominant mechanism underlying corticosteroid-induced disease.IMPORTANCECandida albicans normally lives harmlessly in the mouth, but overgrowth can cause oral candidiasis, a painful infection that can interfere with eating and swallowing. One of the most common causes of oral candidiasis is treatment with corticosteroids, medications that are widely used to control autoimmune and allergic diseases. Although corticosteroids are known to weaken immune defenses, it is unknown which immune pathways are impaired to promote susceptibility to this infection. We show that corticosteroids promote oral candidiasis by suppressing a specific protective immune response, known as type-17 immunity, rather than by triggering excessive inflammatory responses driven by interferon-γ. We further demonstrate that these two immune alterations-loss of type-17 immunity and interferon-γ-driven inflammation-cause oral candidiasis through independent mechanisms. These findings clarify how corticosteroids predispose patients to oral candidiasis and refine our understanding of the immune pathways that normally protect the oral mucosa.