Detrimental Effect of Type I IFNs During Acute Lung Infection With Is Mediated Through the Stimulation of Neutrophil NETosis.
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.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Decker, Anna Sophie
MetadataShow full item record
AbstractPseudomonas aeruginosa is an opportunistic multidrug-resistant pathogen, able to grow in biofilms. It causes life-threatening complications in diseases characterized by the up-regulation of type I interferon (IFN) signaling, such as cancer or viral infections. Since type I IFNs regulate multiple functions of neutrophils, which constitute the first line of anti-bacterial host defense, in this work we aimed to study how interferon-activated neutrophils influence the course of P. aeruginosa infection of the lung. In lungs of infected IFN-sufficient WT mice, significantly elevated bacteria load was observed, accompanied by the prominent lung tissue damage. At the same time IFN-deficient animals seem to be partly resistant to the infection. Lung neutrophils from such IFN-deficient animals release significantly lower amounts of neutrophil extracellular traps (NETs) and reactive oxygen species (ROS), as compared to WT neutrophils. Of note, such IFN-deficient neutrophils show significantly decreased capacity to stimulate biofilm formation by P. aeruginosa. Reduced biofilm production impairs in turn the survival of bacteria in a lung tissue. In line with that, treatment of neutrophils with recombinant IFN-β enhances their NETosis and stimulates biofilm formation by Pseudomonas after co-incubation with such neutrophils. Possibly, bacteria utilizes neutrophil-derived NETs as a scaffold for released biofilms. In agreement with this, in vivo treatment with ROS-scavengers, NETs disruption or usage of the bacterial strains unable to bind DNA, suppress neutrophil-mediated biofilm formation in the lungs. Together, our findings indicate that the excessive activation of neutrophils by type I IFNs leads to their boosted NETosis that in turn triggers biofilm formation by P. aeruginosa and supports its persistence in the infected lung. Targeting these mechanisms could offer a new therapeutic approach to prevent persistent bacterial infections in patients with diseases associated with the up-regulation of type I IFNs.
CitationFront Immunol. 2019 Sep 11;10:2190. doi: 10.3389/fimmu.2019.02190. eCollection 2019.
AffiliationHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
JournalFrontiers in Immunology
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- Neutrophil Extracellular Traps Confine Pseudomonas aeruginosa Ocular Biofilms and Restrict Brain Invasion.
- Authors: Thanabalasuriar A, Scott BNV, Peiseler M, Willson ME, Zeng Z, Warrener P, Keller AE, Surewaard BGJ, Dozier EA, Korhonen JT, Cheng LI, Gadjeva M, Stover CK, DiGiandomenico A, Kubes P
- Issue date: 2019 Apr 10
- Swimming Motility Mediates the Formation of Neutrophil Extracellular Traps Induced by Flagellated Pseudomonas aeruginosa.
- Authors: Floyd M, Winn M, Cullen C, Sil P, Chassaing B, Yoo DG, Gewirtz AT, Goldberg JB, McCarter LL, Rada B
- Issue date: 2016 Nov
- Release of cystic fibrosis airway inflammatory markers from Pseudomonas aeruginosa-stimulated human neutrophils involves NADPH oxidase-dependent extracellular DNA trap formation.
- Authors: Yoo DG, Winn M, Pang L, Moskowitz SM, Malech HL, Leto TL, Rada B
- Issue date: 2014 May 15
- Hypertonic Saline Suppresses NADPH Oxidase-Dependent Neutrophil Extracellular Trap Formation and Promotes Apoptosis.
- Authors: Nadesalingam A, Chen JHK, Farahvash A, Khan MA
- Issue date: 2018
- Compromised host defense on Pseudomonas aeruginosa biofilms: characterization of neutrophil and biofilm interactions.
- Authors: Jesaitis AJ, Franklin MJ, Berglund D, Sasaki M, Lord CI, Bleazard JB, Duffy JE, Beyenal H, Lewandowski Z
- Issue date: 2003 Oct 15