Here, we demonstrated an in vivo requirement of both NLRP3 and NLRP12 for inflammasome formation and caspase-1 activation during in vivo infection with P. chabaudi. We also report that symptomatic infection with either P. falciparum or P. vivax leads to enhanced expression of inflammasome related genes and caspase-1 activation. Here, NLRP12 is linked to infection.