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Mannosylated liposomal CpG\u2010ODN was more effective than liposomal or free CpG\u2010ODN in inhibiting amastigote multiplication within macrophages. Moreover, in a 60\u2010day mouse model of visceralleishmaniasis, complete elimination of spleen parasite burden was achieved by mannosylated liposomal CpG\u2010ODN, compared to 62% and 81% parasite suppression by free and liposomal ODN, respectively, at a similar dose. Although <jats:italic>in vitro<\/jats:italic> exposure of CpG\u2010ODN did not induce marked nitric oxide (NO) generation by macrophages, considerably enhanced amount of NO was generated by macrophages ofCpG\u2010ODN\u2010treated animals. Their splenocytes secreted soluble factors required for the induction of NO generation, and the increased NO generation was paralleled by an increase in antileishmanial activity. Inducible NO generation was suppressed by treating splenocyte supernatants with anti\u2010IFN\u2010\u03b3 or anti\u2010IL\u201012 antibodies, whereas <jats:italic>in vivo<\/jats:italic> administration of these anti\u2010cytokine Ab along with CpG\u2010ODN reversed protection against infection. CpG\u2010ODN treatment resulted in reduced levels of IL\u20104, but increased levels of IFN\u2010\u03b3, IL\u201012 and inducible NO synthase in infected spleen cells, which was magnified by encapsulation in mannose\u2010coated liposomes. This targeted treatment was not only curative, but it also imparted resistance to reinfection. These results represent a general approach for intracellular targeting of CpG\u2010ODN, which effectively enhances its therapeutic potential in redirecting curative Th1 responses in Th2\u2010driven disorders.<\/jats:p>","DOI":"10.1002\/eji.200323671","type":"journal-article","created":{"date-parts":[[2003,5,27]],"date-time":"2003-05-27T16:03:22Z","timestamp":1054051402000},"page":"1508-1518","source":"Crossref","is-referenced-by-count":39,"title":["Targeting of immunostimulatory DNA cures experimental visceral leishmaniasis through nitric oxide up\u2010regulation and T\u2004cell activation"],"prefix":"10.1002","volume":"33","author":[{"given":"Neeta","family":"Datta","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Snigdha","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lopamudra","family":"Das","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pijush\u2004K.","family":"Das","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,5,7]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1080\/00034983.1995.11813013"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830250913"},{"key":"e_1_2_7_3_2","first-page":"1","article-title":"Regulator and effector functions of T\u2004cell subsets in human Leishmania infections.","volume":"68","author":"Kemp M.","year":"1997","journal-title":"APMIS Suppl."},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5416.951"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199802)28:02<669::AID-IMMU669>3.0.CO;2-N"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200010)30:10<2935::AID-IMMU2935>3.0.CO;2-Q"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1089\/107999000312748"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/35047123"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.7.2879"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(99)00048-5"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1006\/clin.1997.4380"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.177.4.1199"},{"key":"e_1_2_7_13_2","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.4049\/jimmunol.162.4.2291","article-title":"Bacterial DNA containing CpG motifs stimulates lymphocyte\u2010dependent protection of mice against lethal infection with intracellular bacteria.","volume":"162","author":"Elkins K. 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