Allergens abrogate antiinflammatory DNA effects and unmask macrophage-driven neutrophilic asthma via ILC2/STING/TNF-α signaling.

ABSTRACT: The mechanisms of neutrophilic and mixed neutrophilic-eosinophilic asthma are poorly understood. We found that extracellular DNA and nucleosomes (Nucs) were elevated in the airways of patients with neutrophilic-eosinophilic asthma and correlated with bronchoalveolar lavage neutrophils. Bronchial tissue from neutrophilic-eosinophilic asthma had more DNA sensor-positive cells. Intranasally administered DNA did not induce airway hyperreactivity (AHR) or any pathology but induced AHR and neutrophilic-eosinophilic inflammation when coadministered with the allergen Alternaria (Alt). Nuc alone induced antiinflammatory/defensive genes, whereas the Nuc-Alt combination increased levels of TNF-α and innate cytokines. The Alt-Nuc phenotype was abolished in Cgas-/-, ALR-/-, Sting-/-, LysMCre:Stingfl/fl

SUBMITTER: Sripada A 

PROVIDER: S-EPMC12352889 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature