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Publication : Cutting edge: IL-1β processing during Pseudomonas aeruginosa infection is mediated by neutrophil serine proteases and is independent of NLRC4 and caspase-1.

First Author  Karmakar M Year  2012
Journal  J Immunol Volume  189
Issue  9 Pages  4231-5
PubMed ID  23024281 Mgi Jnum  J:190602
Mgi Id  MGI:5449289 Doi  10.4049/jimmunol.1201447
Citation  Karmakar M, et al. (2012) Cutting edge: IL-1beta processing during Pseudomonas aeruginosa infection is mediated by neutrophil serine proteases and is independent of NLRC4 and caspase-1. J Immunol 189(9):4231-5
abstractText  To examine the role of caspase-1 and the NLRC4 inflammasome during bacterial infection, C57BL/6, IL-1beta(-/-), caspase-1(-/-), and NLRC4(-/-) mouse corneas were infected with ExoS/T- or ExoU-expressing Pseudomonas aeruginosa. We found that IL-1beta was essential for neutrophil recruitment and bacterial clearance and was produced by myeloid cells rather than resident cells. In addition, neutrophils were found to be the primary source of mature IL-1beta during infection, and there was no significant difference in IL-1beta processing between C57BL/6 and caspase-1(-/-) or NLRC4(-/-) infected corneas. IL-1beta cleavage by human and mouse neutrophils was blocked by serine protease inhibitors and was impaired in infected neutrophil elastase (NE)(-/-) corneas. NE(-/-) mice also had an impaired ability to clear the infection. Together, these results demonstrate that during P. aeruginosa infection, neutrophils are the primary source of mature IL-1beta and that IL-1beta processing is dependent on serine proteases and not NLRC4 or caspase-1.
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