Cutting Edge: IL-1β Processing during Pseudomonas aeruginosa Infection Is Mediated by Neutrophil Serine Proteases and Is Independent of NLRC4 and Caspase-1

To examine the role of caspase-1 and the NLRC4 inflammasome during bacterial infection, C57BL/6, IL-1 beta(-/-), caspase-1(-/-), and NLRC4(-/-) mouse corneas were infected with ExoS/T- or ExoU-expressing Pseudomonas aeruginosa. We found that IL-1 beta 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-1 beta during infection, and there was no significant difference in IL-1 beta processing between C57BL/6 and caspase-1(-/-) or NLRC4(-/-) infected corneas. IL-1 beta 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-1 beta and that IL-1 beta processing is dependent on serine proteases and not NLRC4 or caspase-1. The Journal of Immunology, 2012, 189:4231-4235.