ArticlePLoS neglected tropical diseases2025
IL-18 favors Th2 responses in sporotrichosis caused by Sporothrix globosa, prolonging the course of the disease.
Article in PLoS neglected tropical diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed.
- Article
- The Roles of Interleukin-18 in Inflammation and Autoimmune Disease.Clinical reviews in allergy & immunology · 2026Review
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Authors and funding
7 authors.
Funding
Abstract
backgroundSporotrichosis is a subcutaneous mycosis caused by members of the genus Sporothrix, among which Sporothrix globosa (S. globosa) is the predominant etiological agent in Asia. T cell immunity plays crucial roles in fungal infections, yet the local T cell immune profile in sporotrichosis lesions remains unclear. IL-18, a pleiotropic cytokine capable of modulating T cell responses, is also poorly understood in host defense against S. globosa. METHODOLOGY/PRINCIPAL
findingsqPCR, western blot, and IHC/mIHC were employed to profile IL-18, IL-18 BP, caspase-1 and IL-18R axis, along with Th1,Th2, and Th17 cells and their specific cytokines in sporotrichosis lesions versus healthy skin. Cellular sources of IL-18 in the lesions were identified via mIHC, and IL-18 production from keratinocyte/PBMCs exposed to S. globosa in vitro was tested by qPCR and western blot. Flow cytometry was performed to evaluate the role of IL-18 in Th2 polarization in the PBMCs-S. globosa coculture system. Lesional skin exhibited hyperactivated IL-18 signaling, marked by upregulated IL-18, caspase-1, and IL-18R, alongside decreased IL-18 BP. IL-18 was primarily released by dermal dendritic cells and Langerhans cells, rather than keratinocytes. A mixed Th1/Th2/Th17 microenvironment with Th2 predominance correlated strongly with prolonged disease duration. Strikingly, IL-18 synergistically interacted with Th1-derived IL-2 to establish a self-reinforcing Th2 loop, as evidenced by the strong correlation between lesional IL-4 and IL-18 levels (r = 0.70) and the concomitant upregulation of IL-18/IL-2 during S. globosa-induced Th2 expansion in PBMCs-an effect reversed by IL-18/IL-2 neutralizing antibodies. Critically, this Th2 skewing was mechanistically dependent on NF-κB signaling, as demonstrated through pharmacological pathway inhibition. CONCLUSIONS/SIGNIFICANCE: This study unveils the dual role of IL-18 in human sporotrichosis caused by S. globosa-amplifying both Th1 and Th2 responses but ultimately driving pathogenic Th2 polarization through IL-2 crosstalk. Our work identifies IL-18/IL-2/NF-κB axis as a key Th2-polarizing mechanism driving chronicity in this disease. Targeting this axis could recalibrate anti-fungal immunity, offering translational strategies for this subcutaneous disease.
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