[ODP-135/W6-4] E. coli-derived CirA relayed by extracellular vesicles induce inflammatory responses in macrophages
Patients with the leaky gut syndrome (LGS) occasionally exhibit fever and inflammation without bacterial infection. One possible reason for this is that bacterial outer membrane vesicles (OMVs) cause inflammation without living bacteria. Indeed, we previously found that OMVs of Escherichia coli stimulate inflammatory responses in macrophages (Mφ), and, in turn, the stimulated Mφ release exosomes that induce the inflammatory responses in naive Mφ. In the present study, we tried to identify key factors contained in OMVs and Mφ-dirived exosomes that mediate the inflammatory stimulation from E. coli to naive Mφ.
Proteome analyses of exosomes from Mφ treated with or without the living or heat-killed bacteria revealed 63 candidates of bacterial proteins specifically contained in exosomes of Mφ that were sensitized by the living bacteria. Of these, we picked up four candidates (OmpC, FepA, CirA, and DegP), examined E. coli mutants deficient in each gene, and found that CirA was relayed from OMVs to exosomes to induce the inflammatory responses of naive Mφ. CirA is an outer membrane protein with a β-barrel structure, in which its N-terminal region is encased. We are currently trying to identify the region of CirA, which is responsible for the induction of inflammatory responses in Mφ. CirA may be a therapeutic target for the bacterium-negative inflammation like that observed in LGS.