Abstract
In mice, defense against an intraperitoneal Salmonella infection depends on a vigorous innate immune response. Mutations which lead to an inadequate early response to the pathogen thus identify genes involved in innate immunity. The best studied host resistance factor, NRAMP-1, is an endosomal membrane protein whose loss leads to an inability of the animals to hold the infection in check. However, innate defense against Salmonella is not restricted to mechanisms which directly attack the pathogen within macrophages. Here we have examined the contribution of the LBP, CD14 and TLR4 gene products to innate defense against Salmonella. To this end, we have generated mice which carry a wild-type allele of NRAMP-1, but which are deficient for the LBP, CD14 or TLR4 genes. Loss of any of these genes leads to a susceptibility to Salmonella as dramatic as that seen in animals lacking functional NRAMP-1 protein. This indicates that LBP, CD14 and TLR4 are all critical elements required in the proper induction of this innate defense system.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acute-Phase Proteins / physiology
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Alleles
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Animals
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Base Pair Mismatch
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Base Sequence
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Carrier Proteins / genetics
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Carrier Proteins / physiology*
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Cation Transport Proteins / genetics
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Cation Transport Proteins / metabolism
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Drosophila Proteins*
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Lipopolysaccharide Receptors / genetics
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Lipopolysaccharide Receptors / immunology
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Lipopolysaccharide Receptors / physiology*
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / immunology
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Membrane Glycoproteins / physiology*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Inbred CBA
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Mice, Knockout
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Molecular Sequence Data
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Mutation
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Peritoneum / microbiology*
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Peritoneum / pathology
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Peritonitis / genetics
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Peritonitis / immunology
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Peritonitis / pathology
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / immunology
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Receptors, Cell Surface / physiology*
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Salmonella Infections, Animal / genetics
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Salmonella Infections, Animal / immunology*
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Salmonella Infections, Animal / pathology
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Salmonella typhimurium / pathogenicity
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Toll-Like Receptor 4
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Toll-Like Receptors
Substances
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Acute-Phase Proteins
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Carrier Proteins
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Cation Transport Proteins
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Drosophila Proteins
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Lipopolysaccharide Receptors
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Membrane Glycoproteins
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Receptors, Cell Surface
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Toll-Like Receptor 4
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Toll-Like Receptors
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lipopolysaccharide-binding protein
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natural resistance-associated macrophage protein 1