Gene expression profiling reveals unique pathways associated with differential severity of lyme arthritis.
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-kappaB-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.
Crandall
Hillary
H
Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East, , Salt Lake City, UT 84112, USA.
Dunn
Diane M
DM
Ma
Ying
Y
Wooten
R Mark
RM
Zachary
James F
JF
Weis
John H
JH
Weiss
Robert B
RB
Weis
Janis J
JJ
D000818:Animals; D025065:Borrelia burgdorferi / Q000276:immunology*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D008193:Lyme Disease / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction