Chlamydia muridarum Infection of Macrophages Stimulates IL-1β Secretion and Cell Death via Activation of Caspase-1 in an RIP3-Independent Manner

Chlamydiae are Gram-negative bacteria, which replicate exclusively in the infected host cells. Infection of the host cells by Chlamydiae stimulates the innate immune system leading to an inflammatory response, which is manifested not only by secretion of proinflammatory cytokines such as IL-1 beta from monocytes, macrophages, and dendritic cells, but also possibly by cell death mediated by Caspase-1 pyroptosis. RIP3 is a molecular switch that determines the development of necrosis or inflammation. However, the involvement of RIP3 in inflammasome activation by Chlamydia muridarum infection has not been clarified. Here, we assessed the role of RIP3 in synergy with Caspase-1 in the induction of IL-1 beta production in BMDM after either LPS/ATP or Chlamydia muridarum stimulation. The possibility of pyroptosis and necroptosis interplays and the role of RIP3 in IL-1 beta production during Chlamydia muridarum infection in BMDM was investigated as well. The data indicated that RIP3 is involved in NLRP3 inflammasome activation in LPS/ATP-stimulated BMDMs but not in Chlamydia muridarum infection. Pyroptosis occurred in BMDM after LPS/ATP stimulation or Chlamydia muridarum infection. Moreover, the results also illuminated the important role of the Caspase-1-mediated pyroptosis process which does not involve RIP3. Taken together, these observations may help shed new light on details in inflammatory signaling pathways activated by Chlamydia muridarum infection.