Multiple Pseudomonas species secrete exolysin-like toxins and provoke Caspase-1-dependent macrophage death.
Environ Microbiol
; 19(10): 4045-4064, 2017 10.
Article
en En
| MEDLINE
| ID: mdl-28654176
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-1ß. 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pseudomonas
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Toxinas Bacterianas
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Muerte Celular
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Caspasa 1
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Macrófagos
Límite:
Animals
Idioma:
En
Revista:
Environ Microbiol
Asunto de la revista:
MICROBIOLOGIA
/
SAUDE AMBIENTAL
Año:
2017
Tipo del documento:
Article
País de afiliación:
Francia