Toll-like receptor 4 expression levels determine the degree of 
LPS-susceptibility in mice

Kalis, Christoph; Kanzler, Benoit; Lembo, Annalisa; Poltorak, Alexander; Galanos, Chris; Freudenberg, Marina A.

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Toll-like receptor 4 expression levels determine the degree of LPS-susceptibility in mice

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Kalis, Christoph
Emeritus Group: Cellular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons191144

Kanzler, Benoit
Emeritus Group: Cellular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons191189

Lembo, Annalisa
Emeritus Group: Cellular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons191274

Poltorak, Alexander
Emeritus Group: Cellular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons191064

Galanos, Chris
Emeritus Group: Cellular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons191059

Freudenberg, Marina A.
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

Kalis, C., Kanzler, B., Lembo, A., Poltorak, A., Galanos, C., & Freudenberg, M. A. (2003). Toll-like receptor 4 expression levels determine the degree of LPS-susceptibility in mice. European Journal of Immunology, 33(3), 798-805.

Cite as: https://hdl.handle.net/11858/00-001M-0000-002B-9565-A

Abstract

C57BL/10ScCr (Cr) mice carry a deletion of the Toll-like receptor 4 (tlr4) gene (i.e. they are tlr4^0/0 and are thus refractory to LPS effects. Insertion of wild-type tlr4 transgene into the tlr4^0/0 Cr germ line endowed LPS susceptibility in the two transgenic lines created, indicating that TLR4 is the only limiting factor for LPS responsiveness in Cr mice. The absolute levels of tlr4 mRNA expressed by the heterozygous transgenic (tlr4^Tr/0), wild-type C57BL/10ScSn (Sn) (tlr4^+/+) and heterozygous F1 (Sn x Cr) (tlr4^+/0) mice varied markedly. However, the pattern of distribution of expression in the different organs was the same in all strains. In different biological assays (B cell mitogenicity, cytokine induction and lethal toxicity) the degree of LPS response obtained in the different strains of mice correlated with the levels of tlr4 mRNA expression. In macrophages, investigation of the LPS-induced cytokine (IL-6) response revealed a linear relationship between the response and the logarithm of TLR4-MD-2 levels.