MyD88 plays a unique role in host defense but not arthritis development in Lyme disease.
To assess the contribution of TLR signaling in the host response to Borrelia burgdorferi, mice deficient in the common TLR adaptor protein, myeloid differentiation factor 88 (MyD88), were infected with B. burgdorferi. MyD88-deficient mice harbored extremely high levels of B. burgdorferi in tissues when compared with wild-type littermates and greater amounts of spirochetes in tissues than TLR2-deficient mice. These findings suggest that, in addition to TLR2, other MyD88-dependent pathways play a significant role in the host defense to B. burgdorferi. MyD88(-/-) mice maintained the ability to produce Abs directed against B. burgdorferi. Partial clearance of spirochetes was evident in long term infection studies and immune sera from MyD88-deficient mice were able to protect naive mice from infection with B. burgdorferi. Thus, the acquired immune response appeared to be functional in MyD88(-/-) mice, and the inability to control spirochete numbers was due to a failure of cells involved in innate defenses. Although macrophages from MyD88(-/-) mice responded poorly to Borrelia sonicate in vitro, MyD88(-/-) mice still developed an inflammatory arthritis after infection with B. burgdorferi characterized by an influx of neutrophils and mononuclear cells. The findings presented here point to a dichotomy between the recruitment of inflammatory cells to tissue and an inability of these cells to kill localized spirochetes.
Bolz
Devin D
DD
Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
Sundsbak
Rhianna S
RS
Ma
Ying
Y
Akira
Shizuo
S
Kirschning
Carsten J
CJ
Zachary
James F
JF
Weis
John H
JH
Weis
Janis J
JJ
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology; D000943:Antigens, Differentiation / Q000235:genetics / Q000502:physiology*; D025065:Borrelia burgdorferi / Q000276:immunology / Q000302:isolation & purification; D002478:Cells, Cultured / Q000276:immunology; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D007116:Immunization, Passive; D007249:Inflammation; D008193:Lyme Disease / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000502:physiology; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D016037:Single-Blind Method; D013643:Tarsus, Animal / Q000473:pathology; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors
D048868:Adaptor Proteins, Signal Transducing; D000907:Antibodies, Bacterial; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors