Abstract
Bacterial flagellins are potent inducers of innate immunity. Three signaling pathways have been implicated in the sensing of flagellins; these involve toll-like receptor 5 (TLR5) and the cytosolic proteins Birc1e/Naip5 and Ipaf. Although the structural basis of TLR5-flagellin interaction is known, little is known about how flagellin enters the host cell cytosol to induce signaling via Birc1e/Naip5 and Ipaf. Here we demonstrate for the first time the translocation of bacterial flagellin into the cytosol of host macrophages by the vacuolar pathogen, Salmonella enterica serotype Typhimurium. Translocation of flagellin into the host cell cytosol was directly demonstrated using beta-lactamase reporter constructs. Flagellin translocation required the Salmonella Pathogenicity Island 1 Type III secretion system (SPI-1 T3SS) but not the flagellar T3SS.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Apoptosis Regulatory Proteins / immunology
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Apoptosis Regulatory Proteins / metabolism
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Calcium-Binding Proteins / immunology
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Calcium-Binding Proteins / metabolism
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Cell Line
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Cytosol / immunology
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Cytosol / metabolism
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Cytosol / microbiology
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Flagellin / genetics
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Flagellin / immunology*
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Flagellin / metabolism
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Genomic Islands / genetics
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Genomic Islands / immunology*
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Immunity, Innate / physiology*
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Mice
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Neuronal Apoptosis-Inhibitory Protein / immunology
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Neuronal Apoptosis-Inhibitory Protein / metabolism
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Salmonella Infections / genetics
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Salmonella Infections / immunology*
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Salmonella Infections / metabolism
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Salmonella typhimurium / genetics
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Salmonella typhimurium / immunology*
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Salmonella typhimurium / metabolism
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Signal Transduction / immunology*
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Toll-Like Receptor 5 / immunology
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Toll-Like Receptor 5 / metabolism
Substances
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Apoptosis Regulatory Proteins
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Calcium-Binding Proteins
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Ipaf protein, mouse
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Naip5 protein, mouse
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Neuronal Apoptosis-Inhibitory Protein
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Toll-Like Receptor 5
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Flagellin