Effect of complement component C3 deficiency on experimental Lyme borreliosis in mice.
Mice deficient in complement component C3 (C3(-/-)) and syngeneic C57BL/6 control mice were challenged with Borrelia burgdorferi to determine the role of complement in immune clearance and joint histopathology during experimental Lyme borreliosis. Tibiotarsal joint, ear, and heart tissues were monitored for spirochete numbers at 2, 4, 8, and 12 weeks postinoculation with 10(5) B. burgdorferi B31 clone 5A4 by using quantitative real-time PCR. The spirochete load in joint and ear tissue remained higher in the C3(-/-) mice than in the wild-type counterparts throughout the 12-week study, whereas the numbers in heart tissue of both groups of mice decreased substantially at 8 to 12 weeks postinfection. Histopathology scores for joint tissue were generally higher in the C3(-/-) mice compared to C57BL/6 controls at 2 and 4 weeks postinfection, which may reflect the presence of higher numbers of bacteria in the joints at these early time points. Levels of anti-B. burgdorferi immunoglobulin G tended to be reduced in the C3(-/-) mice compared to control mice. Furthermore, a 5.5-fold-lower number of the complement-sensitive Borrelia garinii was needed to infect C3(-/-) mice compared to C57BL/6 mice, indicating that its sensitivity to complement is one barrier to infection of the mouse model by B. garinii. These results indicate that the complement system may be important in controlling the early dissemination and progression of B. burgdorferi infection.
Lawrenz
Matthew B
MB
Program in Microbiology and Molecular Genetics and Department of Pathology and Laboratory Medicine, Graduate School of Biomedical Sciences, University of Texas-Houston Health Science Center, Houston, Texas, USA.
Wooten
R Mark
RM
Zachary
James F
JF
Drouin
Scott M
SM
Weis
Janis J
JJ
Wetsel
Rick A
RA
Norris
Steven J
SJ
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001483:Base Sequence; D025065:Borrelia burgdorferi / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity; D015169:Colony Count, Microbial; D003176:Complement C3 / Q000172:deficiency* / Q000235:genetics; D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics; D004195:Disease Models, Animal; D007596:Joints / Q000382:microbiology / Q000473:pathology; D008193:Lyme Disease / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013997:Time Factors
D000907:Antibodies, Bacterial; D003176:Complement C3; D004269:DNA, Bacterial