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Clinical and Vaccine Immunology, December 2008, p. 1878-1883, Vol. 15, No. 12
1071-412X/08/$08.00+0     doi:10.1128/CVI.00241-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Lipopolysaccharide-Induced Immune Responses in Relation to the TLR4(Asp299Gly) Gene Polymorphism{triangledown}

Anna Lundberg,1* Lars Andersson Wikberg,1 Jorma Ilonen,2 Outi Vaarala,1,3 and Malin Fagerås Böttcher1

Division of Pediatrics, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköpings Universitet, Linköping, Sweden,1 Laboratory for Immunobiology, Department of Viral Diseases and Immunology, National Public Health Institute, Helsinki, Finland,3 Department of Clinical Microbiology, University of Kuopio, Kuopio, and Immunogenetics Laboratory, University of Turku, Turku, Finland2

Received 4 July 2008/ Returned for modification 28 August 2008/ Accepted 6 October 2008

Altered microbial exposure is a possible explanation for the increase of allergies in the Western world. However, genetic factors influence microbially induced immune responses. We have investigated the TLR4(Asp299Gly) gene polymorphism and its possible association with receptor expression of circulating peripheral blood monocytes and the in vitro cytokine responses and phosphorylation of intracellular signaling proteins in peripheral blood mononuclear cells (PBMC) stimulated with lipopolysaccharide (LPS) from Escherichia coli and Salmonella enterica serotype Typhimurium. We studied 34 of the predominant haplotype TLR4 Asp299 (AA) and 8 heterozygote Asp299Gly (AG) individuals. TLR4 expression levels were similar in the two genotype groups. Serovar Typhimurium LPS induced interleukin-12p70 from PBMC, and the degree of phosphorylation of the intracellular signaling protein I{kappa}B{alpha} in PBMC was lower in the AG than the AA group (P = 0.03 and P = 0.04, respectively). These results were not seen, however, when PMBC were stimulated with E. coli-derived LPS. Based on these results, we propose that TLR4(Asp299Gly) gene polymorphism and the bacterial origin of LPS should be considered when environmental LPS exposure is evaluated in disease risk or protection.

* Corresponding author. Mailing address: Division of Pediatrics, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-58185 Linköping, Sweden. Phone: 46 13 22 35 55. Fax: 46 13 12 74 65. E-mail: anna.lundberg{at}liu.se

{triangledown} Published ahead of print on 15 October 2008.

Clinical and Vaccine Immunology, December 2008, p. 1878-1883, Vol. 15, No. 12
1071-412X/08/$08.00+0     doi:10.1128/CVI.00241-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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