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Bacteroides fragilis signals through Toll-like receptor (TLR) 2 and not through TLR4

Mohammad Alhawi^1,, John Stewart¹, Clett Erridge², Sheila Patrick³ and Ian R. Poxton¹

¹ Medical Microbiology, Centre for Infectious Diseases, University of Edinburgh College of Medicine and Veterinary Medicine, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK

² Department of Cardiovascular Sciences, University of Leicester, Clinical Science Wing, Glenfield General Hospital, Leicester LE3 9QP, UK

³ Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK

Correspondence
Ian R. Poxton
i.r.poxton{at}ed.ac.uk

Received February 2, 2009
Accepted April 9, 2009

Although it is desirable to identify the interactions between endotoxin/LPS and the innate immune mechanism, it is often not possible to isolate these interactions from other cell wall-related structures of protein or polysaccharide origin. There is no universally accepted method to extract different LPSs from different bacteria, and their natural state will be influenced by their interactions with the associated molecules in the bacterial outer membrane. It is now believed that Toll-like receptor (TLR) 4 is the main signal transducer of classical LPS (i.e. Escherichia coli LPS), while TLR2 is used by certain non-classical LPSs. There are contradictory reports as to whether Bacteroides fragilis LPS, a non-classical LPS, signals primarily through TLR2 or TLR4. This study was designed to address this problem. Different non-purified and purified B. fragilis LPSs extracted by different methods together with different heat-killed, whole-cell populations of B. fragilis were used to elucidate the TLR specificity. All of these B. fragilis preparations showed a significant signalling specificity for TLR2 but not for TLR4. This indicates that changing the extraction methods, with or without applying a repurification procedure, and varying the cell populations do not alter the TLR specificity of B. fragilis LPS.

Present address: College of Health Sciences, King Abdulaziz University, PO Box 128098, Jeddah 21362, Saudi Arabia.