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

Yawen Niu1, Qian Wang2, Hao Lin2

  • 1Department 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.

International Immunopharmacology
|June 27, 2026
PubMed
Abstract

Insights

Interleukin-36 gamma (IL-36γ) boosts anti-fungal immunity in the cornea against Aspergillus fumigatus. This cytokine enhances macrophage function, promoting pathogen clearance during fungal keratitis.

Area of Science:

  • Immunology
  • Ophthalmology
  • Microbiology

Background:

  • Fungal keratitis, particularly from Aspergillus fumigatus, poses a significant threat to vision.
  • The role of specific cytokines, like IL-36γ, in corneal immune responses to fungal infections is not fully understood.

Purpose of the Study:

  • To investigate the function of IL-36γ in the context of Aspergillus fumigatus-induced fungal keratitis.
  • To elucidate the mechanisms by which IL-36γ influences macrophage behavior and anti-fungal immunity in the cornea.

Main Methods:

  • Analyzed IL-36γ expression in human fungal keratitis samples and mouse models.
  • Administered recombinant IL-36γ (rmIL-36γ) or IL-36γ siRNA in a mouse model of A. fumigatus keratitis.
  • Assessed macrophage recruitment, CCL-2 expression, IL-6 production, autophagy markers, and phagocytic activity in vitro and in vivo.

Main Results:

  • Aspergillus fumigatus infection upregulated IL-36γ expression in the cornea.
  • rmIL-36γ treatment enhanced macrophage recruitment and CCL-2 production, while IL-36γ siRNA reduced these effects.
  • IL-36γ was found to promote IL-6 production via the Dectin-1/IL-36γ/IL-36R pathway, boost phagocytosis, and enhance autophagic flux in macrophages.

Conclusions:

  • IL-36γ plays a crucial role in enhancing anti-fungal immunity within the cornea during Aspergillus fumigatus infection.
  • Modulation of macrophage function by IL-36γ is a key mechanism contributing to improved fungal clearance.
Keywords:
Aspergillus fumigatusIL-36γKeratitisMacrophage

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