Stat1 deficiency exacerbates carditis but not arthritis during experimental lyme borreliosis.
Activation of the transcription factor Stat1 by interferon-gamma (IFN-gamma) is an important step in the development of antimicrobial effector mechanisms against many bacterial pathogens. Susceptibility to murine Lyme arthritis has been correlated with the production of several proinflammatory cytokines, especially IFN-gamma. To determine the role of IFN-mediated effector mechanisms in the development of Lyme borreliosis, we infected Stat1-deficient mice on both resistant (DBA), and susceptible (C3H) genetic backgrounds. Arthritis in Stat1(/) mice was similar to that of wild-type controls in both mouse strains. Spirochete loads in tissues were also unchanged in Stat1(/) mice. C3H Stat1(/) mice exhibited increased inflammation in the heart, whereas carditis was unchanged in DBA Stat1(/) mice. These results demonstrate that inhibition of macrophage activation and responses to IFN-gamma-mediated signaling do not alter the arthritis resistance or susceptibility phenotype; however, they do affect the severity of carditis in susceptible mouse strains.
Brown
Charles R
CR
Department of Molecular Microbiology, Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA. BrownChar@missouri.edu
Blaho
Victoria A
VA
Fritsche
Kevin L
KL
Loiacono
Christie M
CM
D000818:Animals; D001168:Arthritis / Q000473:pathology*; D015748:Borrelia burgdorferi Group / Q000472:pathogenicity*; D003433:Crosses, Genetic; D008193:Lyme Disease / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D009205:Myocarditis / Q000382:microbiology* / Q000473:pathology*; D050794:STAT1 Transcription Factor / Q000172:deficiency* / Q000235:genetics / Q000276:immunology
D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse