Overexpression of Toll-like receptor 4 amplifies the host response to lipopolysaccharide and provides a survival advantage in transgenic mice
| Autor: | Jean-Martin Lapointe, Line Larivière, Alexandre Benedetto, Magali Beaubier, Line Laroche, Danielle Malo, Bernhard Ryffel, David Torres, Dominic Martel, Franck Bihl, Laurent Salez |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Lipopolysaccharides
Gram-negative bacteria Lipopolysaccharide Transgene Immunology Gene Dosage Mice Transgenic Receptors Cell Surface Lymphocyte Activation Microbiology chemistry.chemical_compound Mice Adjuvants Immunologic Immunology and Allergy Animals Transgenes Receptor Cells Cultured Crosses Genetic Toll-like receptor Mice Inbred C3H Salmonella Infections Animal Innate immune system Membrane Glycoproteins biology Reverse Transcriptase Polymerase Chain Reaction Intracellular parasite Cell Membrane Toll-Like Receptors biology.organism_classification Flow Cytometry Shock Septic Mice Inbred C57BL Survival Rate Toll-Like Receptor 4 chemistry Gene Expression Regulation TLR4 lipids (amino acids peptides and proteins) Injections Intraperitoneal |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 170(12) |
| ISSN: | 0022-1767 |
| Popis: | Toll-like receptors are transmembrane proteins that are involved in the innate immune recognition of microbial constituents. Among them, Toll-like receptor 4 (Tlr4) is a crucial signal transducer for LPS, the major component of Gram-negative bacteria outer cell membrane. The contribution of Tlr4 to the host response to LPS and to infection with virulent Salmonella typhimurium was studied in four transgenic (Tg) strains including three overexpressing Tlr4. There was a good correlation between the level of Tlr4 mRNA expression and the sensitivity to LPS both in vitro and in vivo: Tg mice possessing the highest number of Tlr4 copies respond the most to LPS. Overexpression of Tlr4 by itself appears to have a survival advantage in Tg mice early during infection: animals possessing more than two copies of the gene survived longer and in a greater percentage to Salmonella infection. The beneficial effect of Tlr4 overexpression is greatly enhanced when the mice present a wild-type allele at natural resistance-associated macrophage protein 1, another critical innate immune gene involved in resistance to infection with Salmonella. Tlr4 and natural resistance-associated macrophage protein 1 exhibit functional epistatic interaction to improve the capacity of the host to control bacterial replication. However, this early improvement in disease resistance is not conducted later during infection, because mice overexpressing Tlr4 developed an excessive inflammatory response detrimental to the host. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|