PMID- 28654176 OWN - NLM STAT- MEDLINE DCOM- 20180130 LR - 20210925 IS - 1462-2920 (Electronic) IS - 1462-2912 (Linking) VI - 19 IP - 10 DP - 2017 Oct TI - Multiple Pseudomonas species secrete exolysin-like toxins and provoke Caspase-1-dependent macrophage death. PG - 4045-4064 LID - 10.1111/1462-2920.13841 [doi] AB - Pathogenic bacteria secrete protein toxins that provoke apoptosis or necrosis of eukaryotic cells. Here, we developed a live-imaging method, based on incorporation of a DNA-intercalating dye into membrane-damaged host cells, to study the kinetics of primary bone marrow-derived macrophages (BMDMs) mortality induced by opportunistic pathogen Pseudomonas aeruginosa expressing either Type III Secretion System (T3SS) toxins or the pore-forming toxin, Exolysin (ExlA). We found that ExlA promotes the activation of Caspase-1 and maturation of interleukin-1beta. BMDMs deficient for Caspase-1 and Caspase-11 were resistant to ExlA-induced death. Furthermore, by using KO BMDMs, we determined that the upstream NLRP3/ASC complex leads to the Caspase-1 activation. We also demonstrated that Pseudomonas putida and Pseudomonas protegens and the Drosophila pathogen Pseudomonas entomophila, which naturally express ExlA-like toxins, are cytotoxic toward macrophages and provoke the same type of pro-inflammatory death as does ExlA(+) P. aeruginosa. These results demonstrate that ExlA-like toxins of two-partner secretion systems from diverse Pseudomonas species activate the NLRP3 inflammasome and provoke inflammatory pyroptotic death of macrophages. CI - (c) 2017 Society for Applied Microbiology and John Wiley & Sons Ltd. FAU - Basso, Pauline AU - Basso P AD - CNRS-ERL5261, INSERM, U1036, CEA, Bacterial Pathogenesis and Cellular Responses, Biosciences and Biotechnology Institute of Grenoble, University Grenoble Alpes, France. FAU - Wallet, Pierre AU - Wallet P AD - CIRI, Centre International de Recherche en Infectiologie, INSERM, U1111, Universite Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Superieure de Lyon, Univ Lyon, Lyon, F-69007, France. FAU - Elsen, Sylvie AU - Elsen S AD - CNRS-ERL5261, INSERM, U1036, CEA, Bacterial Pathogenesis and Cellular Responses, Biosciences and Biotechnology Institute of Grenoble, University Grenoble Alpes, France. FAU - Soleilhac, Emmanuelle AU - Soleilhac E AD - CMBA Platform, Biosciences and Biotechnology Institute of Grenoble, University Grenoble Alpes, CEA, INSERM; Genetics & Chemogenomics, France. FAU - Henry, Thomas AU - Henry T AD - CIRI, Centre International de Recherche en Infectiologie, INSERM, U1111, Universite Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Superieure de Lyon, Univ Lyon, Lyon, F-69007, France. FAU - Faudry, Eric AU - Faudry E AD - CNRS-ERL5261, INSERM, U1036, CEA, Bacterial Pathogenesis and Cellular Responses, Biosciences and Biotechnology Institute of Grenoble, University Grenoble Alpes, France. FAU - Attree, Ina AU - Attree I AD - CNRS-ERL5261, INSERM, U1036, CEA, Bacterial Pathogenesis and Cellular Responses, Biosciences and Biotechnology Institute of Grenoble, University Grenoble Alpes, France. LA - eng GR - 311542/ERC_/European Research Council/International PT - Journal Article DEP - 20170726 PL - England TA - Environ Microbiol JT - Environmental microbiology JID - 100883692 RN - 0 (Bacterial Proteins) RN - 0 (Bacterial Toxins) RN - 0 (Inflammasomes) RN - 0 (Interleukin-1beta) RN - 0 (pseudomonas exoprotein A protein, Pseudomonas aeruginosa) RN - EC 3.4.22.36 (Caspase 1) SB - IM MH - Animals MH - Apoptosis MH - Bacterial Proteins/toxicity MH - Bacterial Toxins/*toxicity MH - Bone Marrow Cells MH - Caspase 1/*metabolism MH - *Cell Death MH - Inflammasomes MH - Interleukin-1beta/metabolism MH - Macrophages/*microbiology MH - Mice MH - Mice, Inbred C57BL MH - Pseudomonas/metabolism/*pathogenicity EDAT- 2017/06/28 06:00 MHDA- 2018/01/31 06:00 CRDT- 2017/06/28 06:00 PHST- 2017/04/25 00:00 [received] PHST- 2017/06/02 00:00 [revised] PHST- 2017/06/19 00:00 [accepted] PHST- 2017/06/28 06:00 [pubmed] PHST- 2018/01/31 06:00 [medline] PHST- 2017/06/28 06:00 [entrez] AID - 10.1111/1462-2920.13841 [doi] PST - ppublish SO - Environ Microbiol. 2017 Oct;19(10):4045-4064. doi: 10.1111/1462-2920.13841. Epub 2017 Jul 26.