Journal
JOURNAL OF IMMUNOLOGY
Volume 201, Issue 9, Pages 2767-2775Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1701195
Keywords
-
Categories
Funding
- National Institutes of Health [EY18612]
- Department of Veterans Affairs Merit Award [I01BX002607]
- National Eye Institute Center Core Grant for Vision Research [P30EY011373]
- Research to Prevent Blindness Foundation
Ask authors/readers for more resources
Neutrophils are an important source of IL-1 beta 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-1 beta to the bioactive 17-kDa form. In the current study, we examined the role of IL-1 beta in response to corneal infection with the filamentous fungus Aspergillus fumigatus and found that neutrophils were the predominant source of bioactive IL-1 beta in the cornea. We also observed that caspase-11(-/-) mice exhibit the same susceptibility phenotype as IL-1 beta(-/-), 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-1 beta 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-1 beta processing and secretion in neutrophils activation of Dectin-1 and signaling through the Rail kinase/MEKK rather than the spleen tyrosine kinase pathway. Collectively, these findings reveal unexpected regulation of IL-1 beta production by neutrophils in response to pathogenic fungi.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available