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IL-10 Deficiency Promotes Increased Borrelia burgdorferi Clearance Predominantly through Enhanced Innate Immune Responses¹

Department of Medical Microbiology and Immunology, Medical University of Ohio, Toledo, OH 43614

Borrelia burgdorferi is capable of persistently infecting a variety of hosts despite eliciting potent innate and adaptive immune responses. Preliminary studies indicated that IL-10-deficient (IL-10^–/–) mice exhibit up to 10-fold greater clearance of B. burgdorferi from target tissues compared with wild-type mice, establishing IL-10 as the only cytokine currently known to have such a significant effect on spirochetal clearance. To further delineate these IL-10-mediated immune effects, kinetic studies indicated that spirochete dissemination to target tissues is similar in both wild-type and IL-10^–/– mouse strains, and that enhanced clearance of B. burgdorferi in IL-10^–/– mice is correlated with increased B. burgdorferi-specific Ab as early as 2 wk postinfection. Immunoblot analysis indicated that Abs produced by infected IL-10^–/– and wild-type mice recognize similar ranges of spirochetal Ags. Immune sera from IL-10^–/– and wild-type mice also exhibited similar bactericidal activity in vitro, and passive transfer of these immune sera into B. burgdorferi-infected SCID mice caused similar reductions of bacterial numbers in target tissues. Infectious dose studies indicated that 8-fold more B. burgdorferi were needed to efficiently infect naive IL-10^–/– mice, suggesting these animals possess higher innate barriers to infection. Moreover, macrophages derived from IL-10^–/– mice exhibit enhanced proinflammatory responses to B. burgdorferi stimulation compared with wild-type controls, and these responses are not significantly affected by the presence of immune serum. These findings confirm that B. burgdorferi clearance by innate immune responses is more efficient in the absence of IL-10, and these activities are not directly related to increased levels of B. burgdorferi-specific Ab.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Scientist Development Grant 0335148N from the American Heart Association (to R.M.W.) and start-up funds from the Medical University of Ohio (to R.M.W.).

² Address correspondence and reprint requests to Dr. R. Mark Wooten, Department of Medical Microbiology and Immunology, Medical University of Ohio, 3055 Arlington Avenue, Toledo, OH 43614. E-mail address: rwooten{at}meduohio.edu

³ Abbreviations used in this paper: M, macrophage; H.I., heat inactivation; MOI, multiplicity of infection; Q-PCR, quantitative PCR.

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