Abstract
Venoms consist of a complex mixture of toxic components that are used by a variety of animal species for defense and predation. Envenomation of mammalian species leads to an acute inflammatory response and can lead to the development of IgE-dependent venom allergy. However, the mechanisms by which the innate immune system detects envenomation and initiates inflammatory and allergic responses to venoms remain largely unknown. Here we show that bee venom is detected by the NOD-like receptor family, pyrin domain-containing 3 inflammasome and can trigger activation of caspase-1 and the subsequent processing and unconventional secretion of the leaderless proinflammatory cytokine IL-1β in macrophages. Whereas activation of the inflammasome by bee venom induces a caspase-1-dependent inflammatory response, characterized by recruitment of neutrophils to the site or envenomation, the inflammasome is dispensable for the allergic response to bee venom. Finally, we find that caspase-1-deficient mice are more susceptible to the noxious effects of bee and snake venoms, suggesting that a caspase-1-dependent immune response can protect against the damaging effects of envenomation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis Regulatory Proteins
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Blotting, Western
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Bone Marrow Cells / drug effects
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Bone Marrow Cells / immunology
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Bone Marrow Cells / metabolism
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CARD Signaling Adaptor Proteins
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Carrier Proteins / genetics
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Carrier Proteins / immunology
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Carrier Proteins / metabolism
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Caspase 1 / genetics
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Caspase 1 / immunology
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Caspase 1 / metabolism
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Cell Line, Tumor
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Cells, Cultured
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Crotalid Venoms / immunology
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Crotalid Venoms / toxicity
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / immunology
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Cytoskeletal Proteins / metabolism
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Enzyme Activation / drug effects
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Enzyme Activation / immunology
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Hypersensitivity / genetics
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Hypersensitivity / immunology
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Hypersensitivity / metabolism
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Immunoglobulin E / immunology
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Immunoglobulin E / metabolism
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Inflammasomes / drug effects
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Inflammasomes / immunology*
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Inflammasomes / metabolism
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Inflammation / genetics
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Inflammation / immunology
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Inflammation / metabolism
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Interleukin-1beta / immunology*
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Interleukin-1beta / metabolism
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Macrophages / drug effects
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Macrophages / immunology*
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Macrophages / metabolism
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Mast Cells / drug effects
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Mast Cells / immunology
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Mast Cells / metabolism
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Melitten / immunology
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Melitten / toxicity
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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NLR Family, Pyrin Domain-Containing 3 Protein
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Neutrophils / immunology
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Neutrophils / metabolism
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Receptors, Interleukin-1 / genetics
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Receptors, Interleukin-1 / immunology
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Receptors, Interleukin-1 / metabolism
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Venoms / immunology*
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Venoms / toxicity
Substances
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Apoptosis Regulatory Proteins
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CARD Signaling Adaptor Proteins
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Carrier Proteins
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Crotalid Venoms
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Cytoskeletal Proteins
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Inflammasomes
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Interleukin-1beta
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NLR Family, Pyrin Domain-Containing 3 Protein
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Nlrp3 protein, mouse
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Pycard protein, mouse
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Receptors, Interleukin-1
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Venoms
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Melitten
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Immunoglobulin E
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Caspase 1