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We now demonstrate that induction of the IFN transcriptional profile in<jats:italic>B. burgdorferi<\/jats:italic>-stimulated BMDMs occurs independently of the adapter TRIF and of the cytoplasmic sensor NOD2. In contrast,<jats:italic>B. burgdorferi<\/jats:italic>-induced transcription of these genes was dependent upon a rapid STAT1 feedback amplification pathway. IFN profile gene transcription was IRF3 dependent but did not utilize<jats:italic>B. burgdorferi<\/jats:italic>-derived DNA or DNase-sensitive ligands. Instead, IFN-responsive gene expression could be induced by<jats:italic>B. burgdorferi<\/jats:italic>-derived RNA. Interferon regulatory factor 3 (IRF3)-dependent IFN profile gene transcription was also induced by sonicated bacteria, by the lipoprotein OspA, and by factors released into the BSKII medium during culture of<jats:italic>B. burgdorferi<\/jats:italic>. The IFN-stimulatory activity of<jats:italic>B. burgdorferi<\/jats:italic>culture supernatants was not destroyed by nuclease treatment. Nuclease digestion also had no effect on IFN profile induction mediated by sonicated<jats:italic>B. burgdorferi<\/jats:italic>. Thus,<jats:italic>B. burgdorferi<\/jats:italic>-derived RNA, OspA, and non-nucleic acid ligands present in both sonicated bacteria and<jats:italic>B. burgdorferi<\/jats:italic>culture medium contribute to type I IFN-responsive gene induction. These findings suggest that<jats:italic>B. burgdorferi<\/jats:italic>invasion of joint tissue and the resultant type I IFN induction associated with Lyme arthritis development may involve multiple triggering ligands.<\/jats:p>","DOI":"10.1128\/iai.01070-09","type":"journal-article","created":{"date-parts":[[2010,4,20]],"date-time":"2010-04-20T02:25:59Z","timestamp":1271730359000},"page":"3144-3153","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":37,"title":["The Lyme Disease Spirochete<i>Borrelia burgdorferi<\/i>Utilizes Multiple Ligands, Including RNA, for Interferon Regulatory Factor 3-Dependent Induction of Type I Interferon-Responsive Genes"],"prefix":"10.1128","volume":"78","author":[{"given":"Jennifer C.","family":"Miller","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Utah, Salt Lake City, Utah 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Maylor-Hagen","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Utah, Salt Lake City, Utah 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Utah, Salt Lake City, Utah 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"Weis","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Utah, Salt Lake City, Utah 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janis J.","family":"Weis","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Utah, Salt Lake City, Utah 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80596-8"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03537.x"},{"key":"e_1_3_2_4_2","unstructured":"Current protocols in molecular biology vol. 1"},{"key":"e_1_3_2_5_2","first-page":"521","volume":"57","year":"1984","unstructured":"Barbour, A. 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