Eosinophils release extracellular DNA traps in response to Aspergillus fumigatus

Publication date: Available online 21 September 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Valdirene S. Muniz, Juliana C. Silva, Yasmim A.V. Braga, Rossana C.N. Melo, Shigeharu Ueki, Masahide Takeda, Akira Hebisawa, Koichiro Asano, Rodrigo T. Figueiredo, Josiane S. Neves
BackgroundEosinophils mediate the immune response in different infection 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 human eosinophil ETs (EETs) release. Aspergillus fumigatus (A. fumigatus) is an opportunistic fungus that may cause eosinophilic allergic bronchopulmonary aspergillosis (ABPA). It has been reported that eosinophils are important to the clearance of A. fumigatus in infected mice lungs. However, the immunological mechanisms that underlie the molecular interactions between A. fumigatus and eosinophils are poorly understood.ObjectiveHere, we investigated the presence of EETs in the bronchial mucus plugs of ABPA patients. We also determined whether A. fumigatus-induced human eosinophils EETs release in vitro.MethodsMucus samples of ABPA patients 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.ResultsWe identified abundant nuclear histone-bearing EETs in the bronchial secretions obtained from ABPA patients. In vitro, we demonstrated that A. fumigatus induces EETs release through a mechanism independent of reactive oxygen species but associated to eosinophil death, histone citrullination, CD11b and the Syk tyrosine kinase pathway. EETs lack the killing or fungistatic activities against A. fumigatus.ConclusionOur findings may contribute to the understanding of how eosinophils recognize and act as immune cells in response to A. fumigatus, which may lead to novel insights regarding ABPA patient treatment.

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Teaser

Extracellular DNA traps, commonly found in mucus plugs of patients with allergic bronchopulmonary aspergillosis, are released by eosinophils in response to Aspergillus fumigatus


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