Production of extracellular traps against Aspergillus fumigatus in vitro and in infected lung tissue is dependent on invading neutrophils and influenced by hydrophobin RodA.
Average rating
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Authors
Bruns, SandraKniemeyer, Olaf
Hasenberg, Mike
Aimanianda, Vishukumar
Nietzsche, Sandor
Thywissen, Andreas
Jeron, Andreas
Latgé, Jean-Paul
Brakhage, Axel A
Gunzer, Matthias
Issue Date
2010-04
Metadata
Show full item recordAbstract
Aspergillus fumigatus is the most important airborne fungal pathogen causing life-threatening infections in immunocompromised patients. Macrophages and neutrophils are known to kill conidia, whereas hyphae are killed mainly by neutrophils. Since hyphae are too large to be engulfed, neutrophils possess an array of extracellular killing mechanisms including the formation of neutrophil extracellular traps (NETs) consisting of nuclear DNA decorated with fungicidal proteins. However, until now NET formation in response to A. fumigatus has only been demonstrated in vitro, the importance of neutrophils for their production in vivo is unclear and the molecular mechanisms of the fungus to defend against NET formation are unknown. Here, we show that human neutrophils produce NETs in vitro when encountering A. fumigatus. In time-lapse movies NET production was a highly dynamic process which, however, was only exhibited by a sub-population of cells. NETosis was maximal against hyphae, but reduced against resting and swollen conidia. In a newly developed mouse model we could then demonstrate the existence and measure the kinetics of NET formation in vivo by 2-photon microscopy of Aspergillus-infected lungs. We also observed the enormous dynamics of neutrophils within the lung and their ability to interact with and phagocytose fungal elements in situ. Furthermore, systemic neutrophil depletion in mice almost completely inhibited NET formation in lungs, thus directly linking the immigration of neutrophils with NET formation in vivo. By using fungal mutants and purified proteins we demonstrate that hydrophobin RodA, a surface protein making conidia immunologically inert, led to reduced NET formation of neutrophils encountering Aspergillus fungal elements. NET-dependent killing of Aspergillus-hyphae could be demonstrated at later time-points, but was only moderate. Thus, these data establish that NET formation occurs in vivo during host defence against A. fumigatus, but suggest that it does not play a major role in killing this fungus. Instead, NETs may have a fungistatic effect and may prevent further spreading.Citation
Production of extracellular traps against Aspergillus fumigatus in vitro and in infected lung tissue is dependent on invading neutrophils and influenced by hydrophobin RodA. 2010, 6 (4):e1000873 PLoS Pathog.Affiliation
Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology-Hans-Knoell-Institute (HKI), Jena, Germany.Journal
PLoS pathogensPubMed ID
20442864Type
ArticleLanguage
enISSN
1553-7374ae974a485f413a2113503eed53cd6c53
10.1371/journal.ppat.1000873
Scopus Count
The following license files are associated with this item:
Related articles
- Human Neutrophils Use Different Mechanisms To Kill Aspergillus fumigatus Conidia and Hyphae: Evidence from Phagocyte Defects.
- Authors: Gazendam RP, van Hamme JL, Tool AT, Hoogenboezem M, van den Berg JM, Prins JM, Vitkov L, van de Veerdonk FL, van den Berg TK, Roos D, Kuijpers TW
- Issue date: 2016 Feb 1
- Protein Deiminase 4 and CR3 Regulate Aspergillus fumigatus and β-Glucan-Induced Neutrophil Extracellular Trap Formation, but Hyphal Killing Is Dependent Only on CR3.
- Authors: Clark HL, Abbondante S, Minns MS, Greenberg EN, Sun Y, Pearlman E
- Issue date: 2018
- Proteome Analysis Reveals the Conidial Surface Protein CcpA Essential for Virulence of the Pathogenic Fungus Aspergillus fumigatus.
- Authors: Voltersen V, Blango MG, Herrmann S, Schmidt F, Heinekamp T, Strassburger M, Krüger T, Bacher P, Lother J, Weiss E, Hünniger K, Liu H, Hortschansky P, Scheffold A, Löffler J, Krappmann S, Nietzsche S, Kurzai O, Einsele H, Kniemeyer O, Filler SG, Reichard U, Brakhage AA
- Issue date: 2018 Oct 2
- FleA Expression in Aspergillus fumigatus Is Recognized by Fucosylated Structures on Mucins and Macrophages to Prevent Lung Infection.
- Authors: Kerr SC, Fischer GJ, Sinha M, McCabe O, Palmer JM, Choera T, Lim FY, Wimmerova M, Carrington SD, Yuan S, Lowell CA, Oscarson S, Keller NP, Fahy JV
- Issue date: 2016 Apr
- The RodA hydrophobin on Aspergillus fumigatus spores masks dectin-1- and dectin-2-dependent responses and enhances fungal survival in vivo.
- Authors: Carrion Sde J, Leal SM Jr, Ghannoum MA, Aimanianda V, Latgé JP, Pearlman E
- Issue date: 2013 Sep 1