Neutrophil extracellular traps impair fungal clearance in a mouse model of invasive pulmonary aspergillosis

• Published in: Immunobiology (1979) Vol. 225; no. 1; p. 151867
• Main Authors: Alflen, Astrid, Aranda Lopez, Pamela, Hartmann, Ann-Kathrin, Maxeiner, Joachim, Bosmann, Markus, Sharma, Arjun, Platten, Johannes, Ries, Frederic, Beckert, Hendrik, Ruf, Wolfram, Radsak, Markus P.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier GmbH 01.01.2020
• Subjects: Animals; Apoptosis; Aspergillus fumigatus; Aspergillus fumigatus - physiology; Citrullination - genetics; Disease Models, Animal; Extracellular Traps - metabolism; Humans; Immunity, Innate; Invasive Pulmonary Aspergillosis - immunology; Invasive Pulmonary Aspergillosis - metabolism; Lung - metabolism; Lung - pathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophil extracellular traps; Neutrophils; Neutrophils - immunology; Peptidylarginine deiminase 4; Pneumonia; Protein-Arginine Deiminase Type 4 - genetics; Pneumonia; Aspergillus fumigatus; Peptidylarginine deiminase 4; Neutrophil extracellular traps; Neutrophils
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/j.imbio.2019.11.002

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.