Macrophages infected with Gram-negative bacteria expressing flagellin or Type III secretion system (T3SS) structural proteins are known to activate the NLRC4 inflammasome, resulting in caspase-1 and Gasdermin D (GSDMD) cleavage, IL-1β secretion and pyroptotic cell death. We examined the role of these mediators in IL-1β secretion by neutrophils infected with Pseudomonas aeruginosa strain PAO1 that expresses the Type III secretion system (T3SS) effectors ExoS and ExoT. We found that IL-1β secretion by neutrophils was dependent on expression of the T3SS needle and translocon proteins. Although pro-GSDMD and pro-GSDME were processed in PAO1 infected neutrophils, only GSDMD was required for IL-1β secretion. PAO1 – induced IL-1β secretion by macrophages was NLRC4 dependent, IL-1β secretion by neutrophils utilized NLRC4 only in the absence of P. aeruginosa exoenzymes. Instead, PAO1 – induced IL-1β secretion required NLRP3, which mediated by ExoS ADP ribosyl transferase activity. Overall, these findings reveal fundamental differences between neutrophils and macrophages in IL-1β secretion in response to pathogenic bacteria.