Mycoplasma hyorhinis Activates the NLRP3 Inflammasome and Promotes Migration and Invasion of Gastric Cancer Cells

Background: Mycoplasma hyorhinis (M.hyorhinis, M.hy) is associated with development of gastric and prostate cancers. The NLRP3 inflammasome, a protein complex controlling maturation of important pro-inflammatory cytokines interleukin (IL)-1 beta and IL-18, is also involved in tumorigenesis and metastasis of various cancers. Methodology/Principal Findings: To clarify whether M.hy promoted tumor development via inflammasome activation, we analyzed monocytes for IL-1 beta and IL-18 production upon M.hy challenge. When exposed to M.hy, human monocytes exhibited rapid and robust IL-1 beta and IL-18 secretion. We further identified that lipid-associated membrane protein (LAMP) from M.hy was responsible for IL-1 beta induction. Applying competitive inhibitors, gene specific shRNA and gene targeted mice, we verified that M.hy induced IL-1 beta secretion was NLRP3-dependent in vitro and in vivo. Cathepsin B activity, K+ efflux, Ca2+ influx and ROS production were all required for the NLRP3 inflammasome activation by M.hy. Importantly, it is IL-1 beta but not IL-18 produced from macrophages challenged with M.hy promoted gastric cancer cell migration and invasion. Conclusions: Our data suggest that activation of the NLRP3 inflammasome by M.hy may be associated with its promotion of gastric cancer metastasis, and anti-M.hy therapy or limiting NLRP3 signaling could be effective approach for control of gastric cancer progress.