Dual role of MyD88 in rapid clearance of relapsing fever Borrelia spp. Author(s): Bolz DD (Bolz, Devin D.), Sundsbak RS (Sundsbak, Rhianna S.), Ma Y (Ma, Ying), Akira S (Akira, Shizuo), Weis JH (Weis, John H.), Schwan TG (Schwan, Tom G.), Weis JJ (Weis, Janis J.) Source: INFECTION AND IMMUNITY 74 (12): 6750-6760 DEC 2006
Abstract: 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.
Addresses: Weis JJ (reprint author), Univ Utah, Dept Pathol, 15 N Med Dr E 2100, Salt Lake City, UT 84112 USA Univ Utah, Dept Pathol, Salt Lake City, UT 84112 USA Osaka Univ, Dept Host Def, Res Inst Microbial Dis, Osaka, Japan Natl Inst Hlth, Natl Inst Allergy & Infect Dis, Rocky Mt Labs, Lab Zoonot Pathogens, Hamilton, MT 59840 USA E-mail Addresses: [email protected]