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The work presented here demonstrates that trypanosome DNA activates macrophages to produce factors that may contribute to this response. Initial results demonstrated that<jats:italic>T. brucei rhodesiense<\/jats:italic>DNA was present in the plasma of C57BL\/6 and C57BL\/6-<jats:italic>scid<\/jats:italic>mice following infection. Subsequently, the effect of trypanosome DNA on macrophages was investigated; parasite DNA was found to be less stimulatory than<jats:italic>Escherichia coli<\/jats:italic>DNA but more stimulatory than murine DNA, as predicted by the CG dinucleotide content. Trypanosome DNA stimulated the induction of a signal transduction cascade associated with Toll-like receptor signaling in RAW 264.7 macrophage cells. The signaling cascade led to expression of mRNAs, including interleukin-12 (IL-12) p40, IL-6, IL-10, cyclooxygenase-2, and beta interferon. The treatment of RAW 264.7 cells and bone marrow-derived macrophages with trypanosome DNA induced the production of NO, prostaglandin E<jats:sub>2<\/jats:sub>, and the cytokines IL-6, IL-10, IL-12, and tumor necrosis factor alpha. In all cases, DNase I treatment of<jats:italic>T. brucei rhodesisense<\/jats:italic>DNA abolished the activation. These results suggest that<jats:italic>T. brucei rhodesiense<\/jats:italic>DNA serves as a ligand for innate immune cells and may play an important contributory role in early stimulation of the host immune response during trypanosomiasis.<\/jats:p>","DOI":"10.1128\/iai.01938-05","type":"journal-article","created":{"date-parts":[[2006,7,22]],"date-time":"2006-07-22T00:24:50Z","timestamp":1153527890000},"page":"4530-4537","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":29,"title":["Signal Transduction, Gene Transcription, and Cytokine Production Triggered in Macrophages by Exposure to Trypanosome DNA"],"prefix":"10.1128","volume":"74","author":[{"given":"Tajie H.","family":"Harris","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin Medical School of Medicine and Public Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole M.","family":"Cooney","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin Medical School of Medicine and Public Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Mansfield","sequence":"additional","affiliation":[{"name":"the Bacteriology Department, University of Wisconsin\u2014Madison, Madison, Wisconsin 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna M.","family":"Paulnock","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin Medical School of Medicine and Public Health"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1391"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-7519(01)00170-9"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.11.5423-5432.1998"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.9.3799"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.3.1466"},{"key":"e_1_3_2_7_2","doi-asserted-by":"crossref","first-page":"405","DOI":"10.4049\/jimmunol.130.1.405","volume":"130","year":"1983","unstructured":"Dempsey, W. 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