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Infection and Immunity, March 2008, p. 1153-1162, Vol. 76, No. 3
0019-9567/08/$08.00+0     doi:10.1128/IAI.01404-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Viable Borrelia burgdorferi Enhances Interleukin-10 Production and Suppresses Activation of Murine Macrophages{triangledown}

John J. Lazarus, Maria A. Kay, Akisha L. McCarter, and R. Mark Wooten*

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

Received 18 October 2007/ Returned for modification 19 November 2007/ Accepted 10 December 2007

Although it is capable of eliciting strong innate and adaptive immune responses, Borrelia burgdorferi often evades immune clearance through largely unknown mechanisms. Our previous studies determined that infected interlukin-10–/– (IL-10–/–) mice show significantly lower B. burgdorferi levels than wild-type (B6) mice and that IL-10 inhibits innate immune responses critical for controlling B. burgdorferi infection. To determine whether virulent B. burgdorferi preferentially enhances IL-10 production, we developed an in vitro coculture medium (RPMI.B) in which both B. burgdorferi and primary macrophages (M{phi}s) remain viable. B. burgdorferi grew at similar rates and was able to regulate expression of immunoreactive proteins with similar kinetics in RPMI.B and in traditional BSK medium; in contrast, B. burgdorferi cultured in conventional tissue culture medium (RPMI) rapidly lost viability. Coculture of viable B. burgdorferi in RPMI.B with M{phi}s resulted in more rapid and significant increases in IL-10 transcripts and secreted proteins than coculture with nonviable B. burgdorferi in RPMI, which corresponded with decreased production of proinflammatory cytokines. Addition of live B. burgdorferi to M{phi}s in RPMI.B also elicited substantially higher IL-10 levels than heat-killed bacteria elicited, confirming that increased IL-10 production was not inherent to coculture in RPMI.B. Transfer of supernatants from B. burgdorferi-stimulated M{phi}s into naïve M{phi} 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 substantial upregulation of IL-10 within 24 h of injection of B. burgdorferi. Together, these results suggest that viable B. burgdorferi can suppress early M{phi} responses during infection by causing increased release of IL-10.

* Corresponding author. Mailing address: Department of Medical Microbiology and Immunology, University of Toledo Health Science Campus, 3000 Arlington Ave., Toledo, OH 43614. Phone: (419) 383-6649. Fax: (419) 383-3002. E-mail: R.Mark.Wooten{at}utoledo.edu

{triangledown} Published ahead of print on 17 December 2007.

Editor: B. A. McCormick

Infection and Immunity, March 2008, p. 1153-1162, Vol. 76, No. 3
0019-9567/08/$08.00+0     doi:10.1128/IAI.01404-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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