Neutrophil pyroptosis mediates pathology of P. aeruginosa lung infection in the absence of the NADPH oxidase NOX2

J. C. Ryu, M. J. Kim, Y. Kwon, J. H. Oh, S. S. Yoon, SungJae Shin, J. H. Yoon, J. H. Ryu

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Nod-like receptor family, CARD domain-containing 4 (NLRC4) inflammasome activation is required for efficient clearance of intracellular pathogens through caspsase-1-dependent pyroptosis in macrophages. Although neutrophils have a critical role in protection from Pseudomonas aeruginosa infection, the mechanisms regulating inflammasome-mediated pyroptosis in neutrophils and its physiological role are largely unknown. We sought to determine the specific mechanisms regulating neutrophil pyroptosis in P. aeruginosa strain PAO1 (PAO1) lung infection and to identify the pathological role of this process. Nox2 ' models with reduced neutrophil antibacterial activity exhibited increased neutrophil pyroptosis, which was mediated by flagellin, a pathogenic PAO1 component. We also demonstrate that PAO1-induced pyroptosis depended on NLRC4 and Toll-like receptor 5 (TLR5) in neutrophils generated from Nlrc4 ' or Tlr5 ' mice. Our study reveals previously unknown mechanisms and physiological role of neutrophil pyroptosis during P. aeruginosa lung infection. Furthermore, our findings regarding neutrophil pyroptosis in the context of neutrophil dysfunction may explain the causes of acute and/or chronic infectious diseases discovered in immune-compromised patients.

Original languageEnglish
Pages (from-to)757-774
Number of pages18
JournalMucosal Immunology
Volume10
Issue number3
DOIs
Publication statusPublished - 2017 May 1

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NADPH Oxidase
Neutrophils
Pathology
Lung
Infection
Pseudomonas aeruginosa
Inflammasomes
Toll-Like Receptor 5
Flagellin
Pyroptosis
Pseudomonas Infections
Pathologic Processes
Communicable Diseases
Chronic Disease
Macrophages

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Ryu, J. C. ; Kim, M. J. ; Kwon, Y. ; Oh, J. H. ; Yoon, S. S. ; Shin, SungJae ; Yoon, J. H. ; Ryu, J. H. / Neutrophil pyroptosis mediates pathology of P. aeruginosa lung infection in the absence of the NADPH oxidase NOX2. In: Mucosal Immunology. 2017 ; Vol. 10, No. 3. pp. 757-774.
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Neutrophil pyroptosis mediates pathology of P. aeruginosa lung infection in the absence of the NADPH oxidase NOX2. / Ryu, J. C.; Kim, M. J.; Kwon, Y.; Oh, J. H.; Yoon, S. S.; Shin, SungJae; Yoon, J. H.; Ryu, J. H.

In: Mucosal Immunology, Vol. 10, No. 3, 01.05.2017, p. 757-774.

Research output: Contribution to journalArticle

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