Neutrophil mediated IL-1β processing in Pseudomonas aeruginosa infection is IPAF and Caspase-1 independent and mediated by serine proteases (118.1)
| Autor: | Mausita Karmakar, Yan Sun, Amy Hise, Arne Rietsch, Eric Pearlman |
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| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 188:118.1-118.1 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.188.supp.118.1 |
| Popis: | Inflammasome and caspase-1 dependent cleavage of IL-1β to the mature, active form is the predominant, but not sole mechanism of IL-1β processing. To investigate the role of IL-1β, IPAF/NLRC4 inflammasome and caspase-1 in bacterial keratitis, which is an important worldwide cause of blindness, mouse corneas were infected with Pseudomonas aeruginosa invasive strain PAO1 (expressing ExoS, T and Y but not ExoU), and corneal inflammation and bacterial survival were examined. We found that IL-1β-/- mice had significantly fewer infiltrating neutrophils, and significantly higher CFU than C57BL/6 mice. In contrast, there was no difference in either corneal disease or bacterial survival between caspase-1-/-, IPAF1-/- and C57BL/6 mice. In all mouse strains, we found that neutrophils are the major producers of IL-1β during corneal infection, and that although IL-1β processing by macrophages was completely dependent on caspase-1, neutrophil mediated IL-1β processing in vivo was not impaired in caspase-1-/- or in IPAF1-/- mice. In vitro studies showed that inhibition of neutrophil elastase significantly inhibited IL-1β processing by human and mouse neutrophils. Taken together, these results demonstrate a novel caspase-1 independent mechanism of IL-1β processing by neutrophils during bacterial infection. |
| Databáze: | OpenAIRE |
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