The influence of <i>Aspergillus fumigatus</i> micromycetes on immune response regulation in patients with asthma

Abstract

Aspergillus fumigatus is able not only to sensitize patients with atopy, but also to colonize the respiratory tract, remaining a constant source of allergens due to the small size of the spores and thermal tolerance. Sensitization to A.fumigatus in patients with asthma is associated with a severe course of the disease, and the proliferation of fungal spores in the respiratory tract can lead to the development of allergic bronchopulmonary aspergillosis (ABPA). Currently, the role of micromycetes in the immunopathogenesis of asthma has not been sufficiently studied. The objective was to evaluate the features of the immune response regulation in patients with ABPA or asthma with sensitization to A.fumigatus. The study included 15 patients with ABPA, 10 patients with asthma with sensitization to A. fumigatus, 16 patients with asthma without sensitization to A. fumigatus. The control group consisted of 16 conditionally healthy volunteers. All patients underwent a clinical and functional examination. The Asthma Control Test questionnaire was used to assess disease control. The diagnosis of asthma was established in accordance with the recommendations of the GINA working group (Global Initiative for Asthma, updated, 2022), the diagnosis of fungal sensitization and ABPA in accordance with the recommendations of the ISHAM working group (International Society for Human and Animal Mycology, 2013). The subpopulations of blood lymphocytes were determined by flow cytometry. The A.fumigatus allergen was added to peripheral blood samples to evaluate the production of IFN, IL-10 and IL-13. The levels of cytokines in cell culture supernatants, as well as total IgE, specific IgE (sIgE) to A. fumigatus and thymus and activation-regulated chemokine (TARC) in blood serum were determined by enzyme immunoassay. Significantly higher levels of total IgE, sIgE to A. fumigatus and TARC in blood serum were found in patients with ABPA and asthma with sensitization to A. fumigatus compared to patients with asthma without sensitization to A. fumigatus. The results of immunophenotyping of lymphocytes revealed a significant excess of Th2 memory cells and T-regulatory cells in all patients with asthma compared to the control group. The number of Tfh2 was higher but Th17.1 memory cells were lower in patients with sensitization to A. fumigatus compared to those of conditionally healthy volunteers. Patients with ABPA had significantly higher number of Th2 memory cells and TARC content compared to patients with asthma with sensitization to A. fumigatus. The increased activity of Th2 memory cells is confirmed by increased secretion of IL-13 and IL-10 following decrease in IFN production in response to specific stimulation of blood cells by the fungal allergen compared to the patients with asthma and the control group. A positive correlation was revealed between the number of Th2 memory cells and the levels of sIgE, IgE, TARC, a negative correlation with FEV1. Thus, contact with A. fumigatus significantly enhances the activity of Th2 memory cells in patients with asthma which can lead to a severe course of the disease and the formation of allergic bronchopulmonary aspergillosis. The identified features of the immune response dictate the need for a personalized approach to the choice of therapeutic tactics in this category of patients.