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* Department of Pathology, and
Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112;
Department of Medical Microbiology and Immunology, Medical University of Ohio, Toledo, Ohio 43614; and
Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802
The murine model of Lyme disease provides a unique opportunity to study the localized host response to similar stimulus, Borrelia burgdorferi, in the joints of mice destined to develop severe arthritis (C3H) or mild disease (C57BL/6). Pathways associated with the response to infection and the development of Lyme arthritis were identified by global gene expression patterns using oligonucleotide microarrays. A robust induction of IFN-responsive genes was observed in severely arthritic C3H mice at 1 wk of infection, which was absent from mildly arthritic C57BL/6 mice. In contrast, infected C57BL/6 mice displayed a novel expression profile characterized by genes involved in epidermal differentiation and wound repair, which were decreased in the joints of C3H mice. These expression patterns were associated with disease state rather than inherent differences between C3H and C57BL/6 mice, because C57BL/6-IL-10–/– mice infected with B. burgdorferi develop more severe arthritis than C57BL/6 mice and displayed an early gene expression profile similar to C3H mice. Gene expression profiles at 2 and 4 wk postinfection revealed a common response of all strains that was likely to be important for the host defense to B. burgdorferi and mediated by NF-
B-dependent signaling. The gene expression profiles identified in this study add to the current understanding of the host response to B. burgdorferi and identify two novel pathways that may be involved in regulating the severity of Lyme arthritis.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants (AI-32223 to J.J.W. and J.F.Z.; AR-43521 to J.J.W.; AI-24158 to J.H.W.; and HL-072903 to R.B.W.), National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases Training Grant (DK07115 to H.C.), the American Heart Association (Grant 0335148N to R.M.W.), and by funds from Associated Regional University Pathologists.
2 Address correspondence and reprint requests to Dr. Janis J. Weis, Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East, Room 2100, Salt Lake City, Utah 84112-5650. E-mail address: janis.weis{at}path.utah.edu
3 Abbreviations used in this paper: QTL, quantitative trait loci; SAM, significance analysis of microarray; F, forward; R, reverse; KO, knockout; NC, not changed; MMP, matrix metalloproteinase; TIMP, tissue inhibitor of MMP.
4 The on-line version of this article contains supplemental material.
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