PMID- 12794144
OWN - NLM
STAT- MEDLINE
DCOM- 20030908
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 170
IP  - 12
DP  - 2003 Jun 15
TI  - Overexpression of Toll-like receptor 4 amplifies the host response to 
      lipopolysaccharide and provides a survival advantage in transgenic mice.
PG  - 6141-50
AB  - 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.
FAU - Bihl, Franck
AU  - Bihl F
AD  - Department of Human Genetics, McGill University, and Center for the Study of Host 
      Resistance, Montreal General Hospital, Montreal, Quebec, Canada.
FAU - Salez, Laurent
AU  - Salez L
FAU - Beaubier, Magali
AU  - Beaubier M
FAU - Torres, David
AU  - Torres D
FAU - Lariviere, Line
AU  - Lariviere L
FAU - Laroche, Line
AU  - Laroche L
FAU - Benedetto, Alexandre
AU  - Benedetto A
FAU - Martel, Dominic
AU  - Martel D
FAU - Lapointe, Jean-Martin
AU  - Lapointe JM
FAU - Ryffel, Bernhard
AU  - Ryffel B
FAU - Malo, Danielle
AU  - Malo D
LA  - eng
GR  - 12038-3/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Adjuvants, Immunologic/*biosynthesis/*genetics/physiology
MH  - Animals
MH  - Cell Membrane/genetics/immunology/metabolism
MH  - Cells, Cultured
MH  - Crosses, Genetic
MH  - Flow Cytometry
MH  - Gene Dosage
MH  - Gene Expression Regulation/immunology
MH  - Injections, Intraperitoneal
MH  - Lipopolysaccharides/*administration & dosage/pharmacology
MH  - Lymphocyte Activation/immunology
MH  - Membrane Glycoproteins/*biosynthesis/*genetics/physiology
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Receptors, Cell Surface/*biosynthesis/*genetics/physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Salmonella Infections, Animal/*genetics/immunology/*mortality/pathology
MH  - Shock, Septic/genetics/immunology/mortality
MH  - Survival Rate
MH  - Toll-Like Receptor 4
MH  - Toll-Like Receptors
MH  - Transgenes/immunology
EDAT- 2003/06/10 05:00
MHDA- 2003/09/10 05:00
CRDT- 2003/06/10 05:00
PHST- 2003/06/10 05:00 [pubmed]
PHST- 2003/09/10 05:00 [medline]
PHST- 2003/06/10 05:00 [entrez]
AID - 10.4049/jimmunol.170.12.6141 [doi]
PST - ppublish
SO  - J Immunol. 2003 Jun 15;170(12):6141-50. doi: 10.4049/jimmunol.170.12.6141.