1. Neutrophil extracellular traps impair fungal clearance in a mouse model of invasive pulmonary aspergillosis
- Author
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Joachim Maxeiner, Astrid Alflen, Pamela Aranda Lopez, Johannes Platten, Arjun Sharma, Hendrik Beckert, Wolfram Ruf, Frederic Ries, Markus Bosmann, Ann-Kathrin Hartmann, and Markus P. Radsak
- Subjects
0301 basic medicine ,Neutrophils ,Immunology ,Medizin ,Apoptosis ,Lung injury ,Extracellular Traps ,Article ,Aspergillus fumigatus ,Microbiology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Protein-Arginine Deiminase Type 4 ,In vivo ,medicine ,Animals ,Humans ,Immunology and Allergy ,skin and connective tissue diseases ,Lung ,Invasive Pulmonary Aspergillosis ,Mice, Knockout ,biology ,Wild type ,Hematology ,Neutrophil extracellular traps ,biology.organism_classification ,medicine.disease ,Immunity, Innate ,respiratory tract diseases ,Mice, Inbred C57BL ,Disease Models, Animal ,Pneumonia ,030104 developmental biology ,medicine.anatomical_structure ,Citrullination ,Tumor necrosis factor alpha ,030215 immunology - Abstract
Neutrophil extracellular traps (NETs) are formed by polymorphonuclear neutrophils (PMN) and contribute to the innate host defense by binding and killing bacterial and fungal pathogens. Because NET formation depends on histone hypercitrullination by peptidylarginine deiminase 4 (PAD4), we used PAD4 gene deficient (Pad4-/-) mice in a mouse model of invasive pulmonary aspergillosis (IPA) to address the contribution of NETs to the innate host defense in vivo. After the induction (24 h) of IPA by i.t. infection with Aspergillus fumigatus conidia, Pad4-/- mice revealed lower fungal burden in the lungs, accompanied by less acute lung injury, TNFα and citH3 compared to wildtype controls. These findings suggest that release of NETs contributes to tissue damage and limits control of fungal outgrowth. Thus inhibition of NETosis might be a useful strategy to maintain neutrophil function and avoid lung damage in patients suffering from IPA, especially in those suffering from preexisting pulmonary disease.
- Published
- 2020