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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

Vida A. Dennis,1* Ayanna Jefferson,1 Shree R. Singh,2 Frédéric Ganapamo,3 and Mario T. Philipp1

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 {alpha}. 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.

* Corresponding author. Mailing address: Division of Bacteriology and Parasitology, Tulane National Primate Research Center, 18703 Three Rivers Rd., Covington, LA 70433. Phone: (985) 871-6267. Fax: (985) 871-6390. E-mail: vida{at}tulane.edu.

Editor: D. L. Burns

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.



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