Dual Role of MyD88 in Rapid Clearance of Relapsing FeverBorreliaspp

Abstract

ABSTRACTRelapsing feverBorreliaspp. 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 feverBorrelia. Infected MyD88−/−mice harbored extremely high levels ofB. hermsiiin the blood compared to wild-type littermates. In the comparison of MyD88−/−mice and B- and T-cell-deficientscidmice, two features stood out: (i) bacterial numbers in blood were at least 10-fold greater in MyD88−/−mice thanscidmice, 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 inscidmice. 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 inscidmice. 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 feverBorrelia. This second defect was apparent only when antibody levels were limiting.