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Infection and Immunity, September 2002, p. 4892-4896, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.4892-4896.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Toll-Like Receptor 4 (TLR4)-Deficient Murine Macrophage Cell Line as an In Vitro Assay System To Show TLR4-Independent Signaling of Bacteroides fragilis Lipopolysaccharide

Eva Lorenz,1* Dhavalkumar D. Patel,2 Thomas Hartung,3 and David A. Schwartz4

Department of Internal Medicine, Section of Infectious Diseases, Wake Forest University Medical Center, Winston-Salem,1 Department of Medicine, Section of Allergy and Clinical Immunology,2 Department of Medicine, Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina,4 Department of Pharmacology, University of Konstanz, Konstanz, Germany3

Received 22 February 2002/ Returned for modification 15 May 2002/ Accepted 18 June 2002

Bacterial lipopolysaccharides (LPS) activate cells of innate immunity, such as macrophages, by stimulating signaling through toll-like receptor 4 (TLR4). We and others have hypothesized that LPS derived from different bacterial species may function through TLR4-independent mechanisms. To test this hypothesis, we have generated using a nonviral transformation procedure a bone marrow-derived macrophage cell line called 10ScNCr/23 from mouse strain C57BL/10ScNCr. This mouse strain has a deletion of the TLR4 locus, causing the mouse strain to be nonresponsive to stimulation by LPS from Escherichia coli while responding normally to other bacterial substrates, such as lipoteichoic acid (LTA) from Staphylococcus aureus, which signal TLR4 independently. Stimulation with LTA induces five- and sixfold increases in 10ScNCr/23 cell line tumor necrosis factor alpha and macrophage inflammatory protein-2 (MIP-2) secretion, but no increases in either cytokine were found when cells were stimulated with E. coli LPS. Bacteroides fragilis-derived LPS, however, can effectively stimulate MIP-2 expression in the absence of functional TLR4 in the 10ScNCr/23 cell line. This gives rise to the notion that LPS from some bacterial species will utilize alternative receptors to stimulate the innate immune response.

* Corresponding author. Mailing address: Section of Molecular Medicine and Infectious Diseases, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem NC 27157-1042, Phone: (336) 716-4322. Fax: (336) 716-1214. E-mail: elorenz{at}wfubmc.edu.

Editor: R. N. Moore

Infection and Immunity, September 2002, p. 4892-4896, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.4892-4896.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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