Aspergillus fumigatus induction of IL-33 expression in chronic rhinosinusitis is PAR2-dependent

Caroline J Dietz1,2, Hua Sun1,2, William C Yao1

  • 1Department of Otolaryngology-Head and Neck Surgery, McGovern Medical School at the University of Texas Health Science Center, Houston, Texas, U.S.A.

The Laryngoscope
|April 12, 2019
PubMed
Abstract

Insights

Aspergillus fumigatus protease induces IL-33 in chronic rhinosinusitis with nasal polyps (CRSwNP) via PAR2. This pathway highlights a potential therapeutic target for CRSwNP treatment.

Area of Science:

  • Immunology
  • Microbiology
  • Otorhinolaryngology

Background:

  • Chronic rhinosinusitis with nasal polyps (CRSwNP) involves allergic inflammation driven by IL-13.
  • Aspergillus fumigatus (A. fumigatus) upregulates IL-33 in sinonasal epithelial cells (SNECs), activating innate lymphoid cells.
  • The precise mechanism of A. fumigatus-induced IL-33 expression in CRSwNP remains unclear.

Purpose of the Study:

  • Identify the fungal component(s) responsible for increased IL-33 expression in CRSwNP SNECs.
  • Determine the specific receptor mediating A. fumigatus-induced IL-33 upregulation.
  • Investigate the role of fungal proteases and PAR2 in CRSwNP pathophysiology.

Main Methods:

  • Primary SNECs from CRSwNP patients were stimulated with fungal components.
  • Inhibitors of serine protease and protease-activated receptor 2 (PAR2) were used.
  • IL-33 and PAR2 expression levels were quantified using qRT-PCR and immunohistochemistry.

Main Results:

  • Fungal protease, not cell wall components, elevated IL-33 expression in SNECs.
  • PAR2 expression was significantly higher in inflamed mucosa of CRSwNP patients compared to controls.
  • The increase in IL-33 was dependent on serine protease activity and PAR2 signaling.

Conclusions:

  • A. fumigatus serine protease induces IL-33 expression in CRSwNP SNECs through PAR2.
  • This pathway represents a potential therapeutic target for CRSwNP.
  • Targeting the A. fumigatus protease-PAR2 interaction may reduce allergic inflammation in CRSwNP.

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