FIG 7.

Schematic diagram of inflammasome activation by rickettsiae. This IPA-generated schematic depicts the molecular mechanisms involved in the activation of inflammasome by pathogen-associated molecular patterns during rickettsial infection. R. australis is recognized by and triggers the host’s NLRP3/ASC inflammasome, which leads to caspase-1 activation and secretion of IL-1β and IL-18 and culminates in the control of bacterial replication in macrophages and in vivo. In murine macrophages, whereas NLRP3 is dispensable for inflammasome activation by R. australis, AIM2/ASC is hypothesized to play a role. The priming signal for NLRP3 inflammasome activation is provided by recognition of rickettsial LPS by host TLR4 in both MyD88-dependent and -independent mechanisms. Rickettsiae invade the host cytosol to provide signal 2 for NLRP3/ASC inflammasome through an unknown molecule. Pathways demonstrated in our studies are blue, while mechanisms hypothesized but not tested are gray.