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ZBP1 governs the inflammasome-independent IL-1α and neutrophil inflammation that play a dual role in anti-influenza virus immunity
- Source :
- International Immunology.
- Publication Year :
- 2019
- Publisher :
- Oxford University Press (OUP), 2019.
-
Abstract
- Influenza A virus (IAV) triggers the infected lung to produce IL-1 and recruit neutrophil. Unlike IL-1β, however, little is known about IL-1α in terms of its mechanism of induction, action and physiological relevance to the host immunity against IAV infection. In particular, whether Z-DNA binding protein 1 (ZBP1), a key molecule for IAV-induced cell death, is involved in the IL-1α induction, neutrophil infiltration, and the physiological outcome have not been elucidated. Here we show in murine model that the IAV-induced IL-1α is mediated solely by ZBP1, in an NLRP3-inflammasome-independent manner, and is required for the optimal IL-1β production followed by the formation of neutrophil extracellular traps. During IAV infection, ZBP1 displays a dual role in anti-IAV immune responses mediated by neutrophil, resulting in either protective or pathological outcome in vivo. Thus, ZBP1-mediated IL-1α production is the key initial step of IAV-infected NETs, owing the duality of the consequent lung inflammation.
- Subjects :
- Lung Diseases
0301 basic medicine
Inflammasomes
Neutrophils
Immunology
Inflammation
Biology
medicine.disease_cause
Virus
Mice
03 medical and health sciences
Dogs
0302 clinical medicine
Immune system
Immunity
Interleukin-1alpha
Influenza A virus
medicine
Animals
Immunology and Allergy
Mice, Knockout
Innate immune system
RNA-Binding Proteins
Inflammasome
General Medicine
Neutrophil extracellular traps
Mice, Inbred C57BL
030104 developmental biology
medicine.symptom
030215 immunology
medicine.drug
Subjects
Details
- ISSN :
- 14602377
- Database :
- OpenAIRE
- Journal :
- International Immunology
- Accession number :
- edsair.doi.dedup.....ab4463c51b584bbc983349de0c5cd996