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Infection and Immunity, December 2006, p. 6750-6760, Vol. 74, No. 12
0019-9567/06/$08.00+0     doi:10.1128/IAI.01160-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Dual Role of MyD88 in Rapid Clearance of Relapsing Fever Borrelia spp.

Department of Pathology, University of Utah, Salt Lake City, Utah 84112,¹ Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan,² Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, Hamilton, Montana 59840³

Received 24 July 2006/ Returned for modification 29 August 2006/ Accepted 26 September 2006

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.

Published ahead of print on 9 October 2006.

Editor: F. C. Fang

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