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.
Keywords: ASC, Apoptosis-associated Speck-like protein containing a CARD; BMDM, bone marrow derived macrophages; CFU, colony-forming units; IL, interleukin; IL-1 signaling; IL-17; NLR; NLRP3 inflammasom; NLRP3, NOD-like receptor family, pyrin domain containing 3; NOD-like receptor; Trichophyton rubrum; WT; dermatophytosis; fungal infections; innate immunity; wild-type.