Analysis of the interaction between host and Clostridium botulinum derived membrane vesicles.

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17462
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: Kanazawa University
• Principal Investigator: Kobayashi Nobuhide 金沢大学, 医学系, 助教 (30712799)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: ボツリヌス菌 / 膜小胞 / membrane vesicle / クロストリジウム属

Outline of Final Research Achievements

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 four strains of Clostridium botulinum with those of closely related Clostridium sporogenes and two strains of the symbiont Clostridium 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, essential adaptors for TLRs, and TLR1/2/4. The inhibition of actin polymerization impeded the uptake of MVs in RAW264.7 cells, however, did not reduce the induction of cytokine expression. On the other hand, the inhibition of dynamin or PI3K suppressed the induction of cytokine expression by MVs, suggesting the importance of these factors downstream of TLR signaling.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

ボツリヌス菌の毒素以外の菌体成分が宿主に及ぼす影響は不明であったが、本研究により初めてボツリヌス菌由来MVが自然免疫応答を誘導することを明らかにした。また、複数のクロストリジウム属菌株由来のMVに対する自然免疫応答に共通して重要な受容体および下流のシグナル因子を明らかにした。細菌MVはグラム陰性菌でよく研究されているが、グラム陽性菌、特に嫌気性で扱いにくいクロストリジウム属菌のMVの研究は少なく、本研究で得られた複数のクロストリジウム属菌由来のMVを比較解析した結果は、今後のMV研究およびクロストリジウム属菌研究における基盤的知見となり得る。