Low Th17 cells in patients with cystic fibrosis and allergic broncho-pulmonary aspergillosis

Abstract

Background: Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity response to the allergens of Aspergillus fumigatus, which is the most frequently isolated fungus from the sputum of cystic fibrosis (CF) patients. Because a low number of Th17 lymphocytes is associated with the risk of fungal infections, we investigated inflammatory markers, Th17 cells, and T-cell polarization in CF patients with ABPA. Methods: We analyzed the levels of inflammatory markers, blood counts, chemokines, cytokines, and T cell subsets in blood and sputum of CF subjects to elucidate the immunological factors associated with CF patients with Aspergillus fumigatus (AF) positive sputum (AFS+) or with ABPA. Results: We observed that AFS+ patients have higher sputum and blood IL-6 levels than AF-negative sputum (AFS−) patients. Analysis of blood memory T-helper subsets associated with Th1, Th2, and Th17 polarization among circulating CD45RA−/CD4+ memory T-cell subsets showed higher numbers of CCR4+/CCR6+/CXCR3− and CCR4+/CCR6+/CXCR3+ memory CD4 cells in AFS+ compared to AFS− subjects. Further analysis of Th17-related subsets and IL-17 secreting T cells in subjects with AFS+ showed that those with ABPA have statistically significantly lower levels of Th17 cells as compared to those without ABPA. Conclusion: In CF, AF airway colonization is associated with increased blood counts of Th17-related subsets. However, CF patients with ABPA exhibit lower numbers of CCR4+/CCR6+/CXCR3+ memory CD4 cells and IL-17-secreting CD4 cells compared to control subjects and CF patients without AF sensitization.