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Multiple Pseudomonas species secrete exolysin-like toxins and provoke Caspase-1-dependent macrophage death.

Pauline Basso 1 Pierre Wallet 2 Sylvie Elsen 1 Emmanuelle Soleilhac 3 Thomas Henry 2 Eric Faudry 1 Ina Attrée 1
1 PBRC - Pathogenèse bactérienne et réponses cellulaires
BCI - Biologie du Cancer et de l'Infection, CNRS - Centre National de la Recherche Scientifique : ERL 526
3 GenChem - Genetics and Chemogenomics
BGE - UMR S1038 - Laboratoire de Biologie à Grande Échelle
Abstract : 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-1β. 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.
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Submitted on : Friday, November 2, 2018 - 7:34:05 PM
Last modification on : Thursday, March 26, 2020 - 6:57:49 PM



Pauline Basso, Pierre Wallet, Sylvie Elsen, Emmanuelle Soleilhac, Thomas Henry, et al.. Multiple Pseudomonas species secrete exolysin-like toxins and provoke Caspase-1-dependent macrophage death.. Environmental Microbiology, Wiley-Blackwell, 2017, 10, pp.4045-4064. ⟨10.1111/1462-2920.13841⟩. ⟨hal-01911523⟩



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