Dual role of MyD88 in rapid clearance of relapsing fever Borrelia spp.
Relapsing fever Borrelia spp. undergo antigenic variation, achieve high levels in blood, and require rapid production of immunoglobulin M (IgM) for clearance. MyD88-deficient mice display defective clearance of many pathogens; however, the IgM response to persistent infection is essentially normal. Therefore, MyD88(-/-) mice provided a unique opportunity to study the effect of nonantibody, innate host defenses to relapsing fever Borrelia. Infected MyD88(-/-) mice harbored extremely high levels of B. hermsii in the blood compared to wild-type littermates. In the comparison of MyD88(-/-) mice and B- and T-cell-deficient scid mice, two features stood out: (i) bacterial numbers in blood were at least 10-fold greater in MyD88(-/-) mice than scid mice, even though the production of IgM still occurred in MyD88(-/-) mice; and (ii) many of the MyD88(-/-) mice were able to exert partial clearance, although with delayed kinetics relative to wild-type mice, a feature not seen in scid mice. Further analysis revealed a delay in the IgM response to lipoproteins expressed by the original inoculum; however, by 6 days of infection antibodies were produced in MyD88(-/-) mice that could clear spirochetemia in scid mice. While these results indicated that the production of IgM was delayed in MyD88(-/-) mice, they also point to a second, antibody-independent role for MyD88 signaling in host defense to relapsing fever Borrelia. This second defect was apparent only when antibody levels were limiting.
Bolz
Devin D
DD
Department of Pathology, University of Utah, 15 North Medical Drive East #2100, Salt Lake City, UT 84112, USA.
Sundsbak
Rhianna S
RS
Ma
Ying
Y
Akira
Shizuo
S
Weis
John H
JH
Schwan
Tom G
TG
Weis
Janis J
JJ
D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology; D016470:Bacteremia / Q000235:genetics / Q000276:immunology*; D001898:Borrelia / Q000276:immunology* / Q000302:isolation & purification; D015169:Colony Count, Microbial; D016207:Cytokines / Q000378:metabolism; D007075:Immunoglobulin M / Q000276:immunology; D007700:Kinetics; D008264:Macrophages / Q000276:immunology / Q000469:parasitology; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000502:physiology*; D012061:Relapsing Fever / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000502:physiology
D016207:Cytokines; D007075:Immunoglobulin M; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2