Cytotoxins of the human pathogen Aeromonas hydrophila trigger, via the NLRP3 inflammasome, caspase‐1 activation in macrophages
Copyright policy )Cytotoxins of the human pathogen Aeromonas hydrophila trigger, via the NLRP3 inflammasome, caspase‐1 activation in macrophages
AbstractAeromonas 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.
- GENENTECH INC United States
- Shinshu University Japan
- University of Lausanne Switzerland
- Shinshu University Japan
- University of the Ryukyus Japan
Mice, Knockout, Pore Forming Cytotoxic Proteins, Cell Death, Cytotoxins, Macrophages, Bacterial Toxins, Caspase 1, Immunoblotting, Aeromonas hydrophila, Enzyme Activation, Mice, Inbred C57BL, Hemolysin Proteins, Mice, Caspases, NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Carrier Proteins, Gram-Negative Bacterial Infections
Mice, Knockout, Pore Forming Cytotoxic Proteins, Cell Death, Cytotoxins, Macrophages, Bacterial Toxins, Caspase 1, Immunoblotting, Aeromonas hydrophila, Enzyme Activation, Mice, Inbred C57BL, Hemolysin Proteins, Mice, Caspases, NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Carrier Proteins, Gram-Negative Bacterial Infections
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