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Therefore, we asked whether enhancement of the immune response by artificial stimulation with CpG oligodeoxynucleotide (ODN), a TLR9 agonist, would result in enhanced protection against trypanosomes. In susceptible BALB\/c mice, relative resistance to infection was significantly enhanced by CpG ODN treatment and was associated with decreased parasite burden, increased cytokine production, and elevated parasite-specific B- and T-cell responses. In relatively resistant C57BL\/6 mice, survival was not enhanced but early parasitemia levels were reduced 100-fold and the majority of the parasites were nondividing, short stumpy (SS) forms. CpG ODN treatment of lymphocyte-deficient C57BL\/6-<jats:italic>scid<\/jats:italic>and BALB\/cByJ-<jats:italic>scid<\/jats:italic>mice also enhanced survival and reduced parasitemia, indicating that innate resistance to trypanosome infection can be enhanced. In C57BL\/6-<jats:italic>scid<\/jats:italic>and BALB\/cByJ-<jats:italic>scid<\/jats:italic>mice, the parasites were also predominantly SS forms during the outgrowth of parasitemia. However, the effect of CpG ODN treatment on parasite morphology was not as marked in gamma interferon (IFN-\u03b3)-knockout mice, suggesting that downstream effects of IFN-\u03b3 production may play a discrete role in parasite cell differentiation. Overall, these studies provide the first evidence that enhancement of resistance to African trypanosomes can be induced in susceptible animals in a TLR9-dependent manner and that CpG ODN treatment may influence the developmental life cycle of the parasites.<\/jats:p>","DOI":"10.1128\/iai.01649-06","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T01:28:43Z","timestamp":1173144523000},"page":"2366-2373","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":48,"title":["CpG Oligodeoxynucleotide Treatment Enhances Innate Resistance and Acquired Immunity to African Trypanosomes"],"prefix":"10.1128","volume":"75","author":[{"given":"Tajie H.","family":"Harris","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin\u2014Madison School of Medicine and Public Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Mansfield","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, 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\u2014Madison 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":"10.1098\/rstb.1984.0107"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3024.1989.tb00674.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.3.1466"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"283","DOI":"10.4049\/jimmunol.140.1.283","volume":"140","year":"1988","unstructured":"De Gee, A. 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