A transgenic mouse expressing the human gene for PYRIN domain-only protein 2 (POP2). POP2, when expressed in the transgenic mouse model, broadly dampens inflammatory cytokine production, in part through restricting the activation of both Nlrp3 and Aim2 inflammasomes. POP2 mice exhibit reduced susceptibility to LPS- and bacteria-induced septic shock. Further, POP2 mice are less susceptible to the fatal, acute inflammatory pneumonia caused by pulmonary infection with F. tularensis LVS and F. novicida, which are highly pathogenic to mice, but non-pathogenic to humans.