IL-36γ promotes anti-fungi immunity by regulating macrophage function in the Aspergillus fumigatus keratitis

  • Int Immunopharmacol. 2026 Jun 27:186:117077. doi: 10.1016/j.intimp.2026.117077.
Yawen Niu  1 ,  Qian Wang  2 ,  Hao Lin  2 ,  Lingwen Gu  2 ,  Jing Lin  3 ,  Guiqiu Zhao  4
Affiliations
  • 1. Department of Ophthalmology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, China; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
  • 2. Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
  • 3. Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China. Electronic address: [email protected].
  • 4. Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China. Electronic address: [email protected].
PMID: 42364326 DOI: 10.1016/j.intimp.2026.117077
Abstract

Purpose: To explore the role of IL-36γ in corneas infected by Aspergillus fumigatus (A. fumigatus).

Methods: Expression of IL-36γ was analyzed in 23 Fungal keratitis and 8 healthy donor corneas. C57BL/6 mice corneas were infected with A. fumigatus and IL-36 cytokines expression was assessed. Then, C57BL/6 mice with A. fumigatus keratitis were treated with rmIL-36γ or IL-36γ siRNA to assess CCL-2 expression and macrophage infiltration. In vitro, RAW264.7 macrophages were stimulated with A. fumigatus and pretreated separately with Dectin-1 neutralizing antibody, rmIL-36γ, or IL-36γ siRNA. Expression of IL-6, autophagy-related proteins (LC3-II, Atg7, p62), and phagocytic activity were measured.

Results: A. fumigatus Infection upregulated IL-36γ. rmIL-36γ increased CCL-2 and promoted macrophage recruitment, while IL-36γ siRNA suppressed these responses. In RAW264.7 macrophages, A. fumigatus upregulated IL-6 via the Dectin-1/IL-36γ/IL-36R pathway. Furthermore, IL-36γ boosted phagocytosis. IL-36γ not only promotes autophagosome accumulation but also facilitates autophagic flux.

Conclusion: IL-36γ enhances anti-fungal immunity in the cornea during A. fumigatus Infection by modulating macrophage function.

Keywords
Aspergillus fumigatus; IL-36γ; Keratitis; Macrophage.
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