Aspergillus fumigatus-Specific T Cells in Patients with Chronic Rhinosinusitis
Pascal Ickrath1, Lisa Sprügel1, Niklas Beyersdorf2
1Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University of Würzburg, Würzburg, Germany.
Introduction:
Aspergillus fumigatus belongs to the saprophytic fungi, and its spores form a significant part of the daily load of fungal spores inhaled as particles in aerosols. A. fumigatus is a possible T-cell activator. Its contribution to the pathogenesis of chronic rhinosinusitis (CRS) is controversially discussed. The aim of this study was to detect and characterize A. fumigatus-specific CD4+ and CD8+ T cells in patients with CRS with (CRSwNP) and without (CRSsNP) nasal polyps.
Methods:
Tissue and blood samples were collected from patients who underwent paranasal sinus surgery due to CRSwNP or CRSsNP. Afterward, purified CD4+ and CD8+ cells were cultured together with antigen-presenting cells. A peptide mix derived from A. fumigatus antigen was added to the cultures. After 6 days, multicolor flow cytometry was performed, and proliferation was measured using the marker Ki-67. Cytokine secretion was quantified from the supernatant of the cell culture.
Results:
Significant differences in the proliferation of nasal CD4+ T cells to A. fumigatus antigen were observed for cells from patients with CRSwNP in comparison to CRSsNP, while no differences were found between nasal and peripheral blood T cells. The activation of tissue-derived CD4+ T cells was associated with significantly higher concentrations of IL-4, IL-5, and IL-17a in the cell culture from patients with CRSwNP in comparison to CRSsNP and/or healthy controls.
Conclusion:
Our findings indicate that patients with CRSwNP harbor a higher proportion of A. fumigatus-reactive CD4+ T cells in the nasal mucosa than patients with CRSsNP. A. fumigatus-reactive CD4+ T cells of CRSwNP patients secreted TH2 cytokines and IL-17. Our findings suggest a role for A. fumigatus in the pathogenesis of CRSwNP and provide a rationale for targeted therapies.
Insights
Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have more Aspergillus fumigatus-reactive CD4+ T cells in their nasal lining. These T cells secrete cytokines linked to CRSwNP, suggesting a role for this fungus in the disease.
Area of Science:
- Immunology
- Microbiology
Background:
- Aspergillus fumigatus spores are commonly inhaled.
- The role of A. fumigatus in chronic rhinosinusitis (CRS) pathogenesis is debated.
- This study investigates A. fumigatus-specific T cells in CRS patients.
Purpose of the Study:
- To detect and characterize A. fumigatus-specific CD4+ and CD8+ T cells.
- To compare T cell responses in CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP).
Main Methods:
- Collected tissue and blood samples from CRSwNP and CRSsNP patients.
- Cultured CD4+ and CD8+ T cells with A. fumigatus antigen.
- Measured T cell proliferation (Ki-67) and cytokine secretion (IL-4, IL-5, IL-17a) via flow cytometry.
Main Results:
- CRSwNP patients showed significantly higher nasal CD4+ T cell proliferation to A. fumigatus antigen compared to CRSsNP patients.
- No differences in T cell proliferation were found between nasal and peripheral blood.
- A. fumigatus-reactive CD4+ T cells from CRSwNP patients secreted higher levels of IL-4, IL-5, and IL-17a.
Conclusions:
- CRSwNP patients have an increased proportion of A. fumigatus-reactive CD4+ T cells in nasal mucosa.
- These cells secrete TH2 and IL-17 cytokines, implicating A. fumigatus in CRSwNP pathogenesis.
- Findings support targeted therapies for CRSwNP.
