2. Academic Validation
  3. Locally instructed CXCR4hi neutrophils trigger environment-driven allergic asthma through the release of neutrophil extracellular traps

Locally instructed CXCR4hi neutrophils trigger environment-driven allergic asthma through the release of neutrophil extracellular traps

  • Nat Immunol. 2019 Nov;20(11):1444-1455. doi: 10.1038/s41590-019-0496-9.
Coraline Radermecker  # 1 2 3,  Catherine Sabatel  # 1 3,  Céline Vanwinge 4,  Cecilia Ruscitti 2 3,  Pauline Maréchal 2 3,  Fabienne Perin 4,  Joey Schyns 1 2 3,  Natacha Rocks 4,  Marie Toussaint 5 6,  Didier Cataldo 4,  Sebastian L Johnston 5 6 7,  Fabrice Bureau  # 8 9 10,  Thomas Marichal  # 11 12 13 14
Affiliations

Affiliations

  • 1 Laboratory of Cellular and Molecular Immunology, GIGA Institute, Liege University, Liege, Belgium.
  • 2 Laboratory of Immunophysiology, GIGA Institute, Liege University, Liege, Belgium.
  • 3 Faculty of Veterinary Medicine, Liege University, Liege, Belgium.
  • 4 Laboratory of Tumor and Development Biology, GIGA Institute, Liege University, Liege, Belgium.
  • 5 Airway Disease Section, National Heart and Lung Institute, Imperial College London, London, UK.
  • 6 Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.
  • 7 Imperial College Healthcare National Health Service Trust, London, UK.
  • 8 Laboratory of Cellular and Molecular Immunology, GIGA Institute, Liege University, Liege, Belgium. [email protected].
  • 9 Faculty of Veterinary Medicine, Liege University, Liege, Belgium. [email protected].
  • 10 Walloon Excellence in Life Sciences and Biotechnology, Wallonia, Belgium. [email protected].
  • 11 Laboratory of Cellular and Molecular Immunology, GIGA Institute, Liege University, Liege, Belgium. [email protected].
  • 12 Laboratory of Immunophysiology, GIGA Institute, Liege University, Liege, Belgium. [email protected].
  • 13 Faculty of Veterinary Medicine, Liege University, Liege, Belgium. [email protected].
  • 14 Walloon Excellence in Life Sciences and Biotechnology, Wallonia, Belgium. [email protected].
  • # Contributed equally.
PMID: 31591573 DOI: 10.1038/s41590-019-0496-9
Abstract

Low exposure to microbial products, respiratory viral infections and air pollution are major risk factors for allergic asthma, yet the mechanistic links between such conditions and host susceptibility to type 2 allergic disorders remain unclear. Through the use of single-cell RNA sequencing, we characterized lung neutrophils in mice exposed to a pro-allergic low dose of lipopolysaccharide (LPS) or a protective high dose of LPS before exposure to house dust mites. Unlike exposure to a high dose of LPS, exposure to a low dose of LPS instructed recruited neutrophils to upregulate their expression of the Chemokine Receptor CXCR4 and to release neutrophil extracellular traps. Low-dose LPS-induced neutrophils and neutrophil extracellular traps potentiated the uptake of house dust mites by CD11b+Ly-6C+ dendritic cells and type 2 allergic airway inflammation in response to house dust mites. Neutrophil extracellular traps derived from CXCR4hi neutrophils were also needed to mediate allergic asthma triggered by Infection with Influenza Virus or exposure to ozone. Our study indicates that apparently unrelated environmental risk factors can shape recruited lung neutrophils to promote the initiation of allergic asthma.

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