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Infect. Immun. doi:10.1128/IAI.01404-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Viable Borrelia burgdorferi Enhance Interleukin-10 Production and Suppress Activation of Murine Macrophages

Department of Medical Microbiology and Immunology, University of Toledo Health Science Campus, Toledo, Ohio 43614, USA

^* To whom correspondence should be addressed. Email: R.Mark.Wooten{at}utoledo.edu.

	Abstract

Although capable of eliciting strong innate and adaptive immune responses, Borrelia burgdorferi (Bb) often evades immune clearance through largely unknown mechanisms. Our previous studies determined that infected IL-10^-/- mice show significantly lower Bb levels than wild type (B6) mice, and that IL-10 inhibits innate immune responses critical for controlling Bb infection. To determine whether virulent Bb preferentially enhances IL-10 production, we developed an in vitro co-culture medium (RPMI.B) in which both Bb and primary macrophages (Ms) remain viable. Bb grew at similar rates and was able to regulate expression of immunoreactive proteins with similar kinetics in RPMI.B as bacteria grown in traditional BSK medium; in contrast, Bb cultured in conventional tissue culture medium (RPMI) rapidly lost viability. Co-culture of viable Bb (RPMI.B) with Ms resulted in a more rapid and significant increase in IL-10 transcripts and secreted protein than co-cultures with non-viable Bb (RPMI), which corresponded with decreased production of proinflammatory cytokines. Addition of live Bb to Ms in RPMI.B also elicited substantially higher IL-10 levels than did heat-killed bacteria, confirming that increased IL-10 production was not inherent to co-culture in RPMI.B. Transfer of supernatants from Bb-stimulated Ms onto naïve M cultures resulted in suppressed activation upon subsequent stimulation with different bacterial agonists, and this suppression was obviated by IL-10-specific antibody. In vivo analyses determined that murine skin samples exhibited a substantial upregulation of IL-10 within 24h of Bb injection. Together, these results suggest that viable Bb can suppress early M responses during infection by causing increased release of IL-10.