Interleukin-10 (IL-10) modulates inflammatory responses elicited in vitro and in 
vivo by Borrelia burgdorferi, the Lyme disease spirochete. How IL-10 modulates 
these inflammatory responses still remains elusive. We hypothesize that IL-10 
inhibits effector functions of multiple genes induced by B. burgdorferi in 
macrophages to control concomitantly elicited inflammation. Because macrophages 
are essential in the initiation of inflammation, we used mouse J774 macrophages 
and live B. burgdorferi spirochetes as the model target cell and stimulant, 
respectively. First, we employed transcriptome profiling to identify genes that 
were induced by stimulation of cells with live spirochetes and that were 
perturbed by addition of IL-10 to spirochete cultures. Spirochetes significantly 
induced upregulation of 347 genes at both the 4-h and 24-h time points. IL-10 
inhibited the expression levels, respectively, of 53 and 65 of the 4-h and 24-h 
genes, and potentiated, respectively, at 4 h and 24 h, 65 and 50 genes. 
Prominent among the novel identified IL-10-inhibited genes also validated by 
quantitative real-time PCR (qRT-PCR) were Toll-like receptor 1 (TLR1), TLR2, 
IRAK3, TRAF1, IRG1, PTGS2, MMP9, IFI44, IFIT1, and CD40. Proteome analysis using 
a multiplex enzyme-linked immunosorbent assay (ELISA) revealed the IL-10 
modulation/and or potentiation of RANTES/CCL5, macrophage inflammatory protein 2 
(MIP-2)/CXCL2, IP-10/CXCL10, MIP-1α/CCL3, granulocyte colony-stimulating factor 
(G-CSF)/CSF3, CXCL1, CXCL5, CCL2, CCL4, IL-6, tumor necrosis factor alpha 
(TNF-α), IL-1α, IL-1β, gamma interferon (IFN-γ), and IL-9. Similar results were 
obtained using sonicated spirochetes or lipoprotein as stimulants. Our data show 
that IL-10 alters effectors induced by B. burgdorferi in macrophages to control 
concomitantly elicited inflammatory responses. Moreover, for the first time, 
this study provides global insight into potential mechanisms used by IL-10 to 
control Lyme disease inflammation.