Cytotoxins of the human pathogen Aeromonas hydrophila trigger, via the NLRP3 inflammasome, caspase-1 activation in macrophages.
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.
McCoy
Andrea J
AJ
Division of Bacterial Pathogenesis, Graduate School of Medicine, University of the Ryukyus, Nishiharacho, Okinawa, Japan.
Koizumi
Yukiko
Y
Toma
Claudia
C
Higa
Naomi
N
Dixit
Vishva
V
Taniguchi
Shun'ichiro
S
Tschopp
Jürg
J
Suzuki
Toshihiko
T
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
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