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Journal of Endotoxin Research
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LBP, CD14, TLR4 and the murine innate immune response to a peritoneal Salmonella infection

Martin Bernheiden

Institut für Immunologie und Transfusionsmedizin, Universität Greifswald, Germany

Jan-Michael Heinrich

Institut für Immunologie und Transfusionsmedizin, Universität Greifswald, Germany

Gabriela Minigo

Institut für Immunologie und Transfusionsmedizin, Universität Greifswald, Germany

Christine Schütt

Institut für Immunologie und Transfusionsmedizin, Universität Greifswald, Germany

Felix Stelter

Institut für Immunologie und Transfusionsmedizin, Universität Greifswald, Germany

Mason Freeman

Institut für Immunologie und Transfusionsmedizin, Universität Greifswald, Germany

Douglas Golenbock

Institut für Immunologie und Transfusionsmedizin, Universität Greifswald, Germany

Robert S. Jack

Institut für Immunologie und Transfusionsmedizin, Universität Greifswald, Germany

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.

Journal of Endotoxin Research, Vol. 7, No. 6, 447-450 (2001)
DOI: 10.1177/09680519010070060901
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