PMID- 31708887
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 1664-302X (Print)
IS  - 1664-302X (Electronic)
IS  - 1664-302X (Linking)
VI  - 10
DP  - 2019
TI  - Inflammasome Activation Induced by Perfringolysin O of Clostridium perfringens 
      and Its Involvement in the Progression of Gas Gangrene.
PG  - 2406
LID - 10.3389/fmicb.2019.02406 [doi]
LID - 2406
AB  - Clostridium perfringens (C. perfringens) is Gram-positive anaerobic, 
      spore-forming rod-shaped bacterial pathogen that is widely distributed in nature. 
      This bacterium is known as the causative agent of a foodborne illness and of gas 
      gangrene. While the major virulence factors are the alpha-toxin and perfringolysin O 
      (PFO) produced by type A strains of C. perfringens, the precise mechanisms of how 
      these toxins induce the development of gas gangrene are still not well 
      understood. In this study, we analyzed the host responses to these toxins, 
      including inflammasome activation, using mouse bone marrow-derived macrophages 
      (BMDMs). Our results demonstrated, for the first time, that C. perfringens 
      triggers the activation of caspase-1 and release of IL-1beta through PFO-mediated 
      inflammasome activation via a receptor of the Nod-like receptor (NLR) family, 
      pyrin-domain containing 3 protein (NLRP3). The PFO-mediated inflammasome 
      activation was not induced in the cultured myocytes. We further analyzed the 
      functional roles of the toxins in inducing myonecrosis in a mouse model of gas 
      gangrene. Although the myonecrosis was found to be largely dependent on the 
      alpha-toxin, PFO also induced myonecrosis to a lesser extent, again through the 
      mediation of NLRP3. These results suggest that C. perfringens triggers 
      inflammatory responses via PFO-mediated inflammasome activation via NLRP3, and 
      that this axis contributes in part to the progression of gas gangrene. Our 
      findings provide a novel insight into the molecular mechanisms underlying the 
      pathogenesis of gas gangrene caused by C. perfringens.
CI  - Copyright (c) 2019 Yamamura, Ashida, Okano, Kinoshita-Daitoku, Suzuki, Ohtani, 
      Hamagaki, Ikeda and Suzuki.
FAU - Yamamura, Kiyonobu
AU  - Yamamura K
AD  - Department of Bacterial Pathogenesis, Infection and Host Response, Graduate 
      School of Medical and Dental Sciences, Tokyo Medical and Dental University, 
      Tokyo, Japan.
FAU - Ashida, Hiroshi
AU  - Ashida H
AD  - Department of Bacterial Pathogenesis, Infection and Host Response, Graduate 
      School of Medical and Dental Sciences, Tokyo Medical and Dental University, 
      Tokyo, Japan.
FAU - Okano, Tokuju
AU  - Okano T
AD  - Department of Bacterial Pathogenesis, Infection and Host Response, Graduate 
      School of Medical and Dental Sciences, Tokyo Medical and Dental University, 
      Tokyo, Japan.
FAU - Kinoshita-Daitoku, Ryo
AU  - Kinoshita-Daitoku R
AD  - Department of Bacterial Pathogenesis, Infection and Host Response, Graduate 
      School of Medical and Dental Sciences, Tokyo Medical and Dental University, 
      Tokyo, Japan.
FAU - Suzuki, Shiho
AU  - Suzuki S
AD  - Department of Bacterial Pathogenesis, Infection and Host Response, Graduate 
      School of Medical and Dental Sciences, Tokyo Medical and Dental University, 
      Tokyo, Japan.
FAU - Ohtani, Kaori
AU  - Ohtani K
AD  - Department of Bacteriology and Bacterial Infection, Division of Host Defense 
      Mechanism, Tokai University School of Medicine, Isehara, Japan.
FAU - Hamagaki, Miwako
AU  - Hamagaki M
AD  - Department of Oral Pathology, Graduate School of Medical and Dental Sciences, 
      Tokyo Medical and Dental University, Tokyo, Japan.
FAU - Ikeda, Tohru
AU  - Ikeda T
AD  - Department of Oral Pathology, Graduate School of Medical and Dental Sciences, 
      Tokyo Medical and Dental University, Tokyo, Japan.
FAU - Suzuki, Toshihiko
AU  - Suzuki T
AD  - Department of Bacterial Pathogenesis, Infection and Host Response, Graduate 
      School of Medical and Dental Sciences, Tokyo Medical and Dental University, 
      Tokyo, Japan.
LA  - eng
PT  - Journal Article
DEP - 20191025
PL  - Switzerland
TA  - Front Microbiol
JT  - Frontiers in microbiology
JID - 101548977
PMC - PMC6823607
OTO - NOTNLM
OT  - Clostridium perfringens
OT  - caspase-1
OT  - gas gangrene
OT  - inflammasome
OT  - perfringolysin O
EDAT- 2019/11/12 06:00
MHDA- 2019/11/12 06:01
PMCR- 2019/10/25
CRDT- 2019/11/12 06:00
PHST- 2019/07/24 00:00 [received]
PHST- 2019/10/07 00:00 [accepted]
PHST- 2019/11/12 06:00 [entrez]
PHST- 2019/11/12 06:00 [pubmed]
PHST- 2019/11/12 06:01 [medline]
PHST- 2019/10/25 00:00 [pmc-release]
AID - 10.3389/fmicb.2019.02406 [doi]
PST - epublish
SO  - Front Microbiol. 2019 Oct 25;10:2406. doi: 10.3389/fmicb.2019.02406. eCollection 
      2019.