Monocytes Heterozygous for the Asp299Gly and Thr399Ile Mutations in the Toll-like Receptor 4 Gene Show No Deficit in Lipopolysaccharide Signalling

摘要: Toll-like receptor 4 (TLR4)-mediated recognition of lipopolysaccharide (LPS) is required for efficient 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 inhaled LPS, increased risk bacteraemia sepsis patients reduced atherosclerosis an Italian population. Here we show that monocytes from individuals heterozygous both exhibit no deficit LPS Escherichia coli , Neisseria meningitidis Bacteroides fragilis Yersinia pestis Chlamydia trachomatis Porphyromonas gingivalis or Pseudomonas aeruginosa . We propose relatively high frequency these Caucasian population may reflect modified carriers alternative agonists.