https://orcid.org/0000-0001-9270-0693
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Yan Sun, Serena Abbondante, Mausita Karmakar, Steven de Jesus Carrion, Chengye Che, Amy G Hise, Eric Pearlman, Neutrophil Caspase-11 Is Required for Cleavage of Caspase-1 and Secretion of IL-1β in Aspergillus fumigatus Infection, The Journal of Immunology, Volume 201, Issue 9, November 2018, Pages 2767–2775, https://doi.org/10.4049/jimmunol.1701195
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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.
