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Infection and Immunity, November 2000, p. 6398-6401, Vol. 68, No. 11
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

A Novel Polymorphism in the Toll-Like Receptor 2 Gene and Its Potential Association with Staphylococcal Infection

Eva Lorenz,1,2 Jean Paul Mira,3 Kristyn L. Cornish,1 Nancy C. Arbour,1 and David A. Schwartz1,2,*

Department of Medicine1 and Department of Veterans Affairs Medical Center,2 The University of Iowa, Iowa City, Iowa, and the Medical Intensive Care Unit, Cochin University Hospital, Paris, France3

Received 12 June 2000/Returned for modification 11 August 2000/Accepted 21 August 2000

The toll-like receptor 2 (TLR2) has gained importance as a major mammalian receptor for lipoproteins derived from the cell wall of a variety of bacteria, such as Borrelia burgdorferi, Treponema pallidum, and Mycoplasma fermentans. We were interested in identifying mutations in the TLR2 gene that might prove to be associated with altered susceptibility to septic shock. We performed a mutation screen of the TLR2 gene using single-stranded conformational polymorphism in 110 normal, healthy study subjects and detected an Arg753Gln mutation in three individuals. No other missense mutations were detected in the TLR2 open reading frame. Functional studies demonstrate that the Arg753Gln polymorphism, in comparison to the wild-type TLR2 gene, is significantly less responsive to bacterial peptides derived from B. burgdorferi and T. pallidum. In a septic shock population, the Arg753Gln TLR2 polymorphism occurred in 2 out of 91 septic patients. More importantly, both of the subjects with the TLR2 Arg753Gln polymorphism had staphylococcal infections. These findings suggest that a mutation in the TLR2 gene may predispose individuals to life-threatening bacterial infections.

* Corresponding author. Mailing address: Pulmonary and Critical Care Medicine, Duke University Medical Center, Research Dr., Room 275 MSRB, DUMC Box 2629, Durham, NC 27710. Phone: (919) 668-0380. Fax: (919) 668-0494. E-mail: david.schwartz{at}duke.edu.

Infection and Immunity, November 2000, p. 6398-6401, Vol. 68, No. 11
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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