The role of regulatory T cells (Tregs) on protective immunity in fungal infections, is controversial. Sporotrichosis is an emerging and worldwide-distributed subcutaneous mycosis caused by various related thermodimorphic fungi of the genus Sporothrix. Previously, we showed an elevated percent of Tregs around 21 days post-infection (dpi) in C57BL/6 mice infected with either Sporothrix schenckii or Sporothrix brasiliensis, but the effect of these cells in the ongoing infection was not evaluated. Here, we aim to characterize the role of Foxp3+ Tregs in a subcutaneous S. schenckii infection model. The flow cytometric analyses showed that S. schenckii infection elicited an expansion of a splenic CD4+Foxp3+ population, including a subset of Helios^low+ after ex vivo stimulation with S. schenckii-heat killed yeast. Depletion of Tregs in DEREG mice revealed a reduction of fungal burden in the skin and systemically in liver and kidneys, associated with enhanced Th1 and Th17 responses. Altogether, our results reveal for the first time that Tregs depletion in ongoing S. schenckii infection improves the protective antifungal immunity and these data suggest that Tregs modulation could be explored as a potential therapeutic strategy in sporotrichosis.

调节性 T 细胞 (Tregs) 在真菌感染中对保护性免疫的作用是有争议的。孢子丝菌病是由孢子丝菌属的各种相关热异形真菌引起的一种新兴且全球分布的皮下真菌病。以前，我们在感染申克孢子丝菌或巴西孢子丝菌的C57BL/6 小鼠中，在感染后 21 天左右显示了升高的 Treg 百分比，但未评估这些细胞在持续感染中的作用。在这里，我们旨在表征 Foxp3+ Tregs 在皮下申克感染模型中的作用。流式细胞术分析表明申克链球菌感染引起脾CD4+Foxp3+群体的扩增，包括在用申克链球菌-热杀死酵母离体刺激后的Helios ^low +的亚群。DEREG 小鼠中 Tregs 的消耗表明皮肤和系统性肝脏和肾脏中的真菌负担减少，与增强的 Th1 和 Th17 反应相关。总而言之，我们的结果首次揭示了正在进行的申克链球菌感染中的 Tregs 耗竭提高了保护性抗真菌免疫，这些数据表明 Tregs 调节可以作为孢子丝菌病的潜在治疗策略进行探索。