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Neutrophil Caspase-11 Is Required for Cleavage of Caspase-1 and Secretion of IL-1β in Aspergillus fumigatus Infection.
- Source :
-
Journal of Immunology . 11/1/2018, Vol. 201 Issue 9, p2767-2775. 9p. - Publication Year :
- 2018
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Abstract
- Neutrophils are an important source of IL-1β secretion in bacterial infections, where they infiltrate affected tissues in log-fold higher numbers than macrophages. Neutrophils also have functional NLRP3 and NLRC4 inflammasomes that can process pro- IL-1β to the bioactive 17-kDa form. In the current study, we examined the role of IL-1β in response to corneal infection with the filamentous fungus Aspergillus fumigatus and found that neutrophils were the predominant source of bioactive IL-1β in the cornea. We also observed that caspase-11-/- mice exhibit the same susceptibility phenotype as IL-1β-/-, ASC-/-, NLRP3-/-, and caspase-1-/- mice, with impaired neutrophil recruitment to infected corneas and increased hyphal growth. We further demonstrate that caspase-11 is required for caspase-1 activation and IL-1β processing during infection. In vitro, we show that caspase-11 is regulated by the common type I IFN receptor (IFNAR) through JAK-STAT signaling and that caspase-11 is required for speck formation and caspase-1 activity. Aspergillus spores (conidia) stimulate IL-1β processing and secretion in neutrophils activation of Dectin-1 and signaling through the Raf1 kinase/MEKK rather than the spleen tyrosine kinase pathway. Collectively, these findings reveal unexpected regulation of IL-1β production by neutrophils in response to pathogenic fungi. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00221767
- Volume :
- 201
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- Journal of Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 132763995
- Full Text :
- https://doi.org/10.4049/jimmunol.1701195