title: Cytotoxins of the human pathogen Aeromonas hydrophila trigger, via the NLRP3 inflammasome, caspase-1 activation in macrophages.
abstract: Aeromonas hydrophila is a Gram-negative pathogen that causes serious infectious disease in humans. A. hydrophila induces apoptosis in infected macrophages, but the host proinflammatory responses triggered by macrophage death are largely unknown. Here, we demonstrate that the infection of mouse macrophages with A. hydrophila triggers the activation of caspase-1 and release of IL-1β. Caspase-1 activation was abrogated in macrophages deficient in Nod-like receptor family, pyrin domain containing 3 (NLRP3) and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), but not NLR family, CARD domain containing 4 (NLRC4). The activation of the NLRP3 inflammasome was mediated by three cytotoxins (aerolysin, hemolysin and multifunctional repeat-in-toxin) produced by A. hydrophila. Our results indicated that the NLRP3 inflammasome senses A. hydrophila infection through the action of bacterial cytotoxins.
authors: Division of Bacterial Pathogenesis, Graduate School of Medicine, University of the Ryukyus, Nishiharacho, Okinawa, Japan.
authors: Andrea J
authors: AJ
authors: McCoy
authors: Yukiko
authors: Y
authors: Koizumi
authors: Claudia
authors: C
authors: Toma
authors: Naomi
authors: N
authors: Higa
authors: Vishva
authors: V
authors: Dixit
authors: Shun'ichiro
authors: S
authors: Taniguchi
authors: Jürg
authors: J
authors: Tschopp
authors: Toshihiko
authors: T
authors: Suzuki
mesh_terms: D016980:Aeromonas hydrophila / Q000276:immunology*; D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology*; D020170:Caspase 1 / Q000276:immunology*; D020169:Caspases / Q000276:immunology; D016923:Cell Death / Q000276:immunology; D003603:Cytotoxins / Q000276:immunology*; D004789:Enzyme Activation / Q000276:immunology; D016905:Gram-Negative Bacterial Infections / Q000276:immunology* / Q000382:microbiology; D006460:Hemolysin Proteins / Q000276:immunology; D015151:Immunoblotting; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology
chemical_list: D001427:Bacterial Toxins; D002352:Carrier Proteins; D003603:Cytotoxins; D006460:Hemolysin Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D052899:Pore Forming Cytotoxic Proteins; C032676:aerolysin; D020169:Caspases; D020170:Caspase 1