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Spirochetal lipoproteins initiate expression of NF-\u03baB-dependent cytokines primarily via TLR2, whereas type I interferon (IFN) production is induced through the endosomal receptors TLR7 and TLR9 in human dendritic cells and TLR8 in monocytes. We demonstrate that DNA and RNA are the<jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>components that initiate a type I IFN response by human peripheral blood mononuclear cells (PBMCs). IFN-\u03b1 protein and transcripts for<jats:italic>IRF7<\/jats:italic>,<jats:italic>MX1<\/jats:italic>, and<jats:italic>OAS1<\/jats:italic>were induced by endosomal delivery of<jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>DNA, RNA, or whole-cell lysate, but not by lysate that had been treated with DNase and RNase. Induction of IFN-\u03b1 and IFN-\u03bb1, a type III IFN, by<jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>RNA or live spirochetes required TLR7-dependent signaling and correlated with significantly enhanced transcription and expression of IRF7 but not IRF3. Induction of type I and type III IFNs by<jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>RNA could be completely abrogated by a TLR7 inhibitor, IRS661. In addition to type I and type III IFNs,<jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>RNA contributed to the production of the NF-\u03baB-dependent cytokines, IFN-\u03b3, interleukin-10 (IL-10), IL-1\u03b2, IL-6, and tumor necrosis factor alpha (TNF-\u03b1), by human PBMCs. Collectively, these data indicate that TLR7-dependent recognition of RNA is pivotal for IFN-\u03b1 and IFN-\u03bb1 production by human PBMCs, and that RNA-initiated signaling contributes to full potentiation of the cytokine response generated during<jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>infection.<\/jats:p>","DOI":"10.1128\/iai.01617-14","type":"journal-article","created":{"date-parts":[[2014,3,25]],"date-time":"2014-03-25T05:28:39Z","timestamp":1395725319000},"page":"2405-2416","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":42,"title":["Borrelia burgdorferi RNA Induces Type I and III Interferons via Toll-Like Receptor 7 and Contributes to Production of NF-\u03baB-Dependent Cytokines"],"prefix":"10.1128","volume":"82","author":[{"given":"Andrea C.","family":"Love","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, New York Medical College, Valhalla, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, New York Medical College, Valhalla, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M.","family":"Petzke","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, New York Medical College, Valhalla, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200107123450207"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI21681"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(95)99915-9"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.9.3663-3671.1994"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"2866","DOI":"10.4049\/jimmunol.154.6.2866","article-title":"Treponema pallidum and Borrelia burgdorferi lipoproteins and synthetic lipopeptides activate monocytes\/macrophages","volume":"154","author":"Radolf JD","year":"1995","unstructured":"RadolfJD ArndtLL AkinsDR CurettyLL LeviME ShenY DavisLS NorgardMV. 1995. 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