Monocytes Heterozygous for the Asp299Gly and Thr399Ile Mutations in the Toll-like Receptor 4 Gene Show No Deficit in Lipopolysaccharide Signalling (original) (raw)
Brief Definitive Report| June 09 2003
Department of Medical Microbiology, University of Edinburgh Medical School, Edinburgh, EH8 9AG Scotland, United Kingdom
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Department of Medical Microbiology, University of Edinburgh Medical School, Edinburgh, EH8 9AG Scotland, United Kingdom
Search for other works by this author on:
Department of Medical Microbiology, University of Edinburgh Medical School, Edinburgh, EH8 9AG Scotland, United Kingdom
Search for other works by this author on:
Clett Erridge
Department of Medical Microbiology, University of Edinburgh Medical School, Edinburgh, EH8 9AG Scotland, United Kingdom
John Stewart
Department of Medical Microbiology, University of Edinburgh Medical School, Edinburgh, EH8 9AG Scotland, United Kingdom
Ian R. Poxton
Department of Medical Microbiology, University of Edinburgh Medical School, Edinburgh, EH8 9AG Scotland, United Kingdom
Address correspondence to I.R. Poxton, Medical Microbiology, University of Edinburgh Medical School, Teviot Place, Edinburgh, EH8 9AG Scotland, UK. Phone: 44-131-650-3128; Fax: 44-131-650-3128; E-mail: [email protected]
Received: December 03 2002
Revision Received: April 02 2003
Accepted: April 02 2003
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2003
J Exp Med (2003) 197 (12): 1787–1791.
Received:
December 03 2002
Revision Received:
April 02 2003
Toll-like receptor 4 (TLR4)-mediated recognition of lipopolysaccharide (LPS) is required for efficient recognition of Gram-negative bacterial infections. Two commonly occurring mutations in the human TLR4 gene (Asp299Gly and Thr399Ile) have recently been shown to be associated with blunted physiological responses to inhaled LPS, and with increased risk of Gram-negative bacteraemia in sepsis patients and reduced risk of atherosclerosis in an Italian population. Here we show that monocytes from individuals heterozygous for both mutations in the TLR4 gene exhibit no deficit in recognition of LPS of Escherichia coli, Neisseria meningitidis, Bacteroides fragilis, Yersinia pestis, Chlamydia trachomatis, Porphyromonas gingivalis, or Pseudomonas aeruginosa. We propose that the relatively high frequency of these mutations in the Caucasian population may reflect modified responses of carriers to alternative TLR4 agonists.
The Rockefeller University Press
2003
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