Dual Role of MyD88 in Rapid Clearance of Relapsing Fever<i>Borrelia</i>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.