Eosinophils release extracellular DNA traps in response toAspergillus fumigatus

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Background:Eosinophils mediate the immune response in different infectious conditions. The release of extracellular DNA traps (ETs) by leukocytes has been described as an innate immune response mechanism that is relevant in many disorders including fungal diseases. Different stimuli induce the release of human eosinophil ETs (EETs).Aspergillus fumigatusis an opportunistic fungus that may cause eosinophilic allergic bronchopulmonary aspergillosis (ABPA). It has been reported that eosinophils are important to the clearance ofA fumigatusin infected mice lungs. However, the immunological mechanisms that underlie the molecular interactions betweenA fumigatusand eosinophils are poorly understood.Objective:Here, we investigated the presence of EETs in the bronchial mucus plugs of patients with ABPA. We also determined whetherA fumigatusinduced the release of human eosinophil EETsin vitro.Methods:Mucus samples of patients with ABPA were analyzed by light and confocal fluorescence microscopy. The release of EETs by human blood eosinophils was evaluated using different pharmacological tools and neutralizing antibodies by fluorescence microscopy and a fluorimetric method.Results:We identified abundant nuclear histone-bearing EETs in the bronchial secretions obtained from patients with ABPA.In vitro, we demonstrated thatA fumigatusinduces the release of EETs through a mechanism independent of reactive oxygen species but associated with eosinophil death, histone citrullination, CD11b, and the Syk tyrosine kinase pathway. EETs lack the killing or fungistatic activities againstA fumigatus.Conclusions:Our findings may contribute to the understanding of how eosinophils recognize and act as immune cells in response toA fumigatus, which may lead to novel insights regarding the treatment of patients with ABPA.Graphical abstract

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