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Differential ASC requirements reveal a key role for neutrophils and a noncanonical IL-1β response to Pseudomonas aeruginosa
- Source :
- American journal of physiology. Lung cellular and molecular physiology. 309(8)
- Publication Year :
- 2015
-
Abstract
- The NLRC4 inflammasome is responsible for IL-1β processing by macrophages in response to Pseudomonas aeruginosa infection. We therefore hypothesized that mice that lack ASC, an NLRC4 inflammasome adaptor protein necessary for in vitro IL-1β production by macrophages, would be preferentially protected from a hyperinflammatory lethal challenge that is dependent on bacterial type three secretion system (T3SS) activity. We report herein that lack of ASC does not confer preferential protection in response to P. aeruginosa acute infection and that ASC−/−mice are capable of producing robust amounts of IL-1β comparable with C57BL/6 mice. We now identify that neutrophils represent the ASC-independent source of IL-1β production during the acute phases of infection both in models of acute pneumonia and peritonitis. Consequently, depletion of neutrophils in ASC−/−mice leads to a marked deficit in IL-1β production in vivo. The pulmonary neutrophil IL-1β response is predominantly dependent on caspase-1, which contrasts with data derived from ocular infection. These studies therefore identify a noncanonical mechanism of IL-1β production by neutrophils independent of ASC and demonstrate the first physiological contribution of neutrophils as an important source of IL-1β in response to acute P. aeruginosa infection during acute pneumonia and peritonitis.
- Subjects :
- Pulmonary and Respiratory Medicine
Physiology
Inflammasomes
Neutrophils
Interleukin-1beta
Peritonitis
Inflammation
Biology
In Vitro Techniques
medicine.disease_cause
Type three secretion system
Microbiology
Mice
In vivo
NLRC4
Physiology (medical)
medicine
Pneumonia, Bacterial
Animals
Pseudomonas Infections
Mice, Knockout
Pseudomonas aeruginosa
Calcium-Binding Proteins
Signal transducing adaptor protein
Inflammasome
Cell Biology
Articles
medicine.disease
CARD Signaling Adaptor Proteins
Mice, Inbred C57BL
Disease Models, Animal
Immunology
medicine.symptom
Apoptosis Regulatory Proteins
medicine.drug
Subjects
Details
- ISSN :
- 15221504
- Volume :
- 309
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- American journal of physiology. Lung cellular and molecular physiology
- Accession number :
- edsair.doi.dedup.....6a17d9f5cfe19d1a7426613e9eca8738