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How IL-10 modulates these inflammatory responses still remains elusive. We hypothesize that IL-10 inhibits effector functions of multiple genes induced by<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. burgdorferi<\/jats:named-content>in macrophages to control concomitantly elicited inflammation. Because macrophages are essential in the initiation of inflammation, we used mouse J774 macrophages and live<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. burgdorferi<\/jats:named-content>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-1\u03b1\/CCL3, granulocyte colony-stimulating factor (G-CSF)\/CSF3, CXCL1, CXCL5, CCL2, CCL4, IL-6, tumor necrosis factor alpha (TNF-\u03b1), IL-1\u03b1, IL-1\u03b2, gamma interferon (IFN-\u03b3), and IL-9. Similar results were obtained using sonicated spirochetes or lipoprotein as stimulants. Our data show that IL-10 alters effectors induced by<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. burgdorferi<\/jats:named-content>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.<\/jats:p>","DOI":"10.1128\/iai.05451-11","type":"journal-article","created":{"date-parts":[[2011,9,27]],"date-time":"2011-09-27T06:11:42Z","timestamp":1317103902000},"page":"4876-4892","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":50,"title":["Interleukin-10 Alters Effector Functions of Multiple Genes Induced by Borrelia burgdorferi in Macrophages To Regulate Lyme Disease Inflammation"],"prefix":"10.1128","volume":"79","author":[{"given":"Aarti","family":"Gautam","sequence":"first","affiliation":[{"name":"Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurabh","family":"Dixit","sequence":"additional","affiliation":[{"name":"Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana"},{"name":"Present address: Department of Malaria Vaccine Development Branch NIH\/NIAID, Rockville, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario T.","family":"Philipp","sequence":"additional","affiliation":[{"name":"Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shree R.","family":"Singh","sequence":"additional","affiliation":[{"name":"Center for Nanobiotechnology Research, Alabama State University, Montgomery, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A.","family":"Morici","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Tulane University, Tulane University Health Sciences Center, New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Kaushal","sequence":"additional","affiliation":[{"name":"Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vida A.","family":"Dennis","sequence":"additional","affiliation":[{"name":"Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana"},{"name":"Center for Nanobiotechnology Research, Alabama State University, Montgomery, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm732"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5428.736"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.8.3037-3041.1997"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.2002.tb00623.x"},{"key":"e_1_3_3_6_2","first-page":"959","article-title":"Chronic Lyme borreliosis in the laboratory mouse","volume":"143","author":"Barthold S. 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