[ODP22] 5. Pathogenicity -b. Toxins, effectors and physically active substances

[ODP-132] C. botulinum and related clostridia derived membrane vesicles induce inflammatory responses

Nobuhide Kobayashi¹, Kimihiro Abe², Sachiyo Akagi¹, Sho Amatsu¹, Takuhiro Matsumura¹, Nobuhiko Nomura², Nozomu Obana³, Yukako Fujinaga¹ (¹Dept. Bacteriol., Grad. Sch. Med., Kanazawa Univ., ²Fac. Life Environ. Sci., Univ. Tsukuba, ³TMRC, Fac. Med., Univ. Tsukuba)

Clostridium botulinum produces botulinum neurotoxin complexes that cause botulism. Previous studies elucidated the molecular pathogenesis of botulinum neurotoxin complexes; however, it currently remains unclear whether other components of the bacterium affect host cells. Recent studies provided insights into the role of bacterial membrane vesicles (MVs) produced by some bacterial species in host immunity and pathology. We herein examined and compared the cellular effects of MVs isolated from 4 strains of C. botulinum with those of closely related C. sporogenes, and 2 strains of the symbiont C. scindens. MVs derived from all strains induced inflammatory cytokine expression in intestinal epithelial and macrophage cell lines. Cytokine expression was dependent on MyD88 and TRIF, signal adaptor proteins for Toll-like receptors (TLRs). MVs were phagocytosed by RAW264.7 cells, and the inhibition of phagocytosis did not reduce the induction of cytokine expression. On the other hand, the inhibition of dynamin or phosphatidylinositol-3 kinase (PI3K) suppressed the induction of cytokine expression by MVs, suggesting the importance of these factors downstream of TLR signaling. The present results indicate that MVs from C. botulinum and related clostridial species induce host inflammatory responses.