| First Author | Sun Y | Year | 2018 |
| Journal | J Immunol | Volume | 201 |
| Issue | 9 | Pages | 2767-2775 |
| PubMed ID | 30266768 | Mgi Jnum | J:267678 |
| Mgi Id | MGI:6258030 | Doi | 10.4049/jimmunol.1701195 |
| Citation | Sun Y, et al. (2018) Neutrophil Caspase-11 Is Required for Cleavage of Caspase-1 and Secretion of IL-1beta in Aspergillus fumigatus Infection. J Immunol 201(9):2767-2775 |
| abstractText | Neutrophils are an important source of IL-1beta 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-1beta to the bioactive 17-kDa form. In the current study, we examined the role of IL-1beta in response to corneal infection with the filamentous fungus Aspergillus fumigatus and found that neutrophils were the predominant source of bioactive IL-1beta in the cornea. We also observed that caspase-11(-/-) mice exhibit the same susceptibility phenotype as IL-1beta(-/-), 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-1beta 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-1beta 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-1beta production by neutrophils in response to pathogenic fungi. |
