Yoshikawa Fábio Seiti Yamada, Ferreira Lucas Gonçalves, de Almeida Sandro Rogério
a Faculty of Pharmaceutical Sciences; Department of Clinical e Toxicological Analysis; University of São Paulo ; São Paulo , Brazil.
Virulence. 2015;6(5):449-57. doi: 10.1080/21505594.2015.1020274. Epub 2015 May 7.
Dermatophytosis are one of the most common fungal infections in the world. They compromise keratinized tissues and the main etiological agent is Trichophyton rubrum. Macrophages are key cells in innate immunity and prominent sources of IL-1β, a potent inflammatory cytokine whose main production pathway is by the activation of inflammasomes and caspase-1. However, the role of inflammasomes and IL-1 signaling against T.rubrum has not been reported. In this work, we observed that bone marrow-derived macrophages produce IL-1β in response to T.rubrum conidia in a NLRP3-, ASC- and caspase-1-dependent fashion. Curiously, lack of IL-1 signaling promoted hyphae development, uncovering a protective role for IL-1β in macrophages. In addition, mice lacking IL-1R showed reduced IL-17 production, a key cytokine in the antifungal defense, in response to T.rubrum. Our findings point to a prominent role of IL-1 signaling in the immune response to T.rubrum, opening the venue for the study of this pathway in other fungal infections.
皮肤癣菌病是世界上最常见的真菌感染之一。它们侵袭角质化组织，主要病原体是红色毛癣菌。巨噬细胞是固有免疫中的关键细胞，也是白细胞介素-1β（IL-1β）的主要来源，IL-1β是一种强效炎症细胞因子，其主要产生途径是通过炎性小体和半胱天冬酶-1的激活。然而，炎性小体和IL-1信号通路在抗红色毛癣菌方面的作用尚未见报道。在这项研究中，我们观察到骨髓来源的巨噬细胞以NLRP3、ASC和半胱天冬酶-1依赖的方式对红色毛癣菌分生孢子产生IL-1β。奇怪的是，缺乏IL-1信号通路会促进菌丝生长，这揭示了IL-1β在巨噬细胞中的保护作用。此外，缺乏IL-1受体的小鼠对红色毛癣菌的反应中，关键抗真菌防御细胞因子IL-17的产生减少。我们的研究结果表明IL-1信号通路在抗红色毛癣菌免疫反应中起重要作用，为研究该通路在其他真菌感染中的作用开辟了道路。
