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Infection and Immunity, October 2006, p. 5780-5789, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.00678-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Interleukin-10 Anti-Inflammatory Response to Borrelia burgdorferi, the Agent of Lyme Disease: a Possible Role for Suppressors of Cytokine Signaling 1 and 3

Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana,¹ Department of Math and Science, Alabama State University, Montgomery, Alabama,² Division of Immunology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana³

Received 27 April 2006/ Returned for modification 30 May 2006/ Accepted 25 July 2006

It has been established that interleukin-10 (IL-10) inhibits inflammatory cytokines produced by macrophages in response to Borrelia burgdorferi or its lipoproteins. The mechanism by which IL-10 exerts this anti-inflammatory effect is still unknown. Recent findings indicate that suppressors of cytokine signaling (SOCS) proteins are induced by cytokines and Toll-like receptor (TLR)-mediated stimuli, and in turn they can down-regulate cytokine and TLR signaling in macrophages. Because it is known that SOCS are induced by IL-10 and that B. burgdorferi and its lipoproteins most likely interact via TLR2 or the heterodimers TLR2/1 and/or TLR2/6, we hypothesized that SOCS are induced by IL-10 and B. burgdorferi and its lipoproteins in macrophages and that SOCS may mediate the inhibition by IL-10 of concomitantly elicited cytokines. We report here that mouse J774 macrophages incubated with IL-10 and added B. burgdorferi spirochetes (freeze-thawed, live, or sonicated) or lipidated outer surface protein A (L-OspA) augmented their SOCS1/SOCS3 mRNA and protein expression, with SOCS3 being more abundant. Pam₃Cys, a synthetic lipopeptide, also induced SOCS1/SOCS3 expression under these conditions, but unlipidated OspA was ineffective. Neither endogenous IL-10 nor the translation inhibitor cycloheximide blocked SOCS1/SOCS3 induction by B. burgdorferi and its lipoproteins, indicating that the expression of other genes is not required. This temporally correlated with the IL-10-mediated inhibition of the inflammatory cytokines IL-1ß, IL-6, IL-12p40, IL-18, and tumor necrosis factor . Our data are evidence to suggest that expression of SOCS is part of the mechanism of IL-10-mediated inhibition of inflammatory cytokines elicited by B. burgdorferi and its lipoproteins.

Editor: D. L. Burns

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