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PMID: 16487238 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The Toll-like receptor 4 (Asp299Gly) polymorphism is a risk factor for Gram-negative and haematogenous osteomyelitis.

Clinical and experimental immunology ·Vol. 143 ·No. 3 ·2006-03-00 ·Pages 404-13

Montes AH, Asensi V, Alvarez V, Valle E, Ocaña MG, Meana A, Carton JA, Paz J, Fierer J, Celada A

Abstract

Osteomyelitis is a bone infection caused mostly by Staphylococcus aureus but also by Gram-negative bacteria. Toll-like receptors (TLRs), after recognizing microbial products, induce a signal in neutrophils, leading to NF-kappaB activation and transcription of pro-inflammatory genes. Polymorphisms in TLR2 (Arg753Gln) and TLR4 (Asp299Gly, Thr399Ile) genes are associated with bacterial infections, we therefore studied these polymorphisms in osteomyelitis patients. Homozygotes for the TLR4 (Asp299Gly) polymorphism were significantly more frequent among the 80 osteomyelitis patients than in the 155 healthy controls (3/80, 3.8%versus 0/155, 0%; P = 0.038). Carriers of one or two G alleles of this tlr4 polymorphism were more likely to have Gram-negative, haematogenous and/or chronic osteomyelitis than those without this mutation (P < 0.031). Patients with the TLR4 (Thr399Ile) mutant, which cosegregates with the TLR4 (Asp299Gly), were also carriers of this second polymorphism. No differences for the TLR2 (Arg753Gln) genotypes were found between patients and controls. Neutrophils of patients homozygous for the TLR4 (Asp299Gly) polymorphism showed lower LPS-induced apoptosis reduction, phosphorylation of the inhibitor of NF-kappaB, and lower IL-6 and TNF-alpha levels (P < 0.05). We report here for the first time an association between this TLR4 polymorphism and susceptibility to Gram-negative bacteria and haematogenous osteomyelitis.

MeSH Terms
Adolescent Adult Aged Aged, 80 and over Apoptosis/immunology Cells, Cultured Cytokines/metabolism Female Genetic Predisposition to Disease Genotype Gram-Negative Bacterial Infections/genetics,immunology Humans I-kappa B Proteins/metabolism Male Middle Aged NF-KappaB Inhibitor alpha Neutrophils/immunology Osteomyelitis/genetics,immunology,microbiology Phosphorylation Polymorphism, Genetic Risk Factors Toll-Like Receptor 2/genetics,immunology Toll-Like Receptor 4/genetics,immunology
Chemicals
Cytokines I-kappa B Proteins NFKBIA protein, human TLR2 protein, human Toll-Like Receptor 2 Toll-Like Receptor 4 NF-KappaB Inhibitor alpha
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Montes A H
Department of Biochemistry and Molecular Biology, Oviedo University Medical School and Hospital Central de Asturias, Oviedo, Spain.
Asensi Victor
Alvarez Victoria
Valle Eulalia
Ocaña M G
Meana A
Carton J A
Paz Jose
Fierer J
Celada A
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Article Info
Journal
Clinical and experimental immunology
Abbr.
Clin Exp Immunol
ISSN
0009-9104
DOI
10.1111/j.1365-2249.2005.03002.x
Published
2006-03-00
Pages
404-13
Language
English
Region
England
NLM ID
0057202
PMCID
PMC1809620
Subset
IM
External Links
PubMed source DOI: 10.1111/j.1365-2249.2005.03002.x PMC Full Text View journal details
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