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To determine if this mechanism involves gamma interferon (IFN-\u03b3)-induced activation and\/or specific IFN-\u03b3-regulated macrophage leishmanicidal mechanisms (generation of reactive nitrogen or oxygen intermediates, we treated gene-deficient mice infected with<jats:italic>Leishmania donovani<\/jats:italic>. In IFN-\u03b3 gene knockout (GKO) mice, Sb inhibited but did not kill intracellular<jats:italic>L. donovani<\/jats:italic>(2% killing versus 76% in controls). Sb was active (&gt;94% killing), however, in both inducible nitric oxide synthase (iNOS) knockout (KO) and respiratory burst (phagocyte oxidase)-deficient chronic granulomatous disease (X-CGD) mice. Sb's efficacy was also maintained in doubly deficient animals (X-CGD mice treated with an iNOS inhibitor). In contrast to Sb, amphotericin B (AmB) induced high-level killing in GKO mice; AmB was also fully active in iNOS KO and X-CGD animals. Although resolution of<jats:italic>L. donovani<\/jats:italic>infection requires iNOS, residual visceral infection remained largely suppressed in iNOS KO mice treated with Sb or AmB. These results indicate that endogenous IFN-\u03b3 regulates the leishmanicidal response to Sb and achieves this effect via a pathway unrelated to the macrophage's primary microbicidal mechanisms. The role of IFN-\u03b3 is selective, since it is not a cofactor in the response to AmB. Treatment with either Sb or AmB permits an iNOS-independent mechanism to emerge and control residual intracellular<jats:italic>L. donovani<\/jats:italic>infection.<\/jats:p>","DOI":"10.1128\/iai.68.1.288-293.2000","type":"journal-article","created":{"date-parts":[[2009,5,1]],"date-time":"2009-05-01T17:57:25Z","timestamp":1241200645000},"page":"288-293","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":91,"title":["Roles of Endogenous Gamma Interferon and Macrophage Microbicidal Mechanisms in Host Response to Chemotherapy in Experimental Visceral Leishmaniasis"],"prefix":"10.1128","volume":"68","author":[{"given":"Henry W.","family":"Murray","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Department of Medicine, Weill Medical College of Cornell University, New York, New York 10021"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharmaine","family":"Delph-Etienne","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Medicine, Weill Medical College of Cornell University, New York, New York 10021"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1985.34.270"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.7.2564-2569.1997"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/159.1.113"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00933004"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.11.1.154"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/314896"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90085-3"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.23.040183.001511"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.3.1058-1063.1994"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.8.1825"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"351","DOI":"10.4049\/jimmunol.129.1.351","article-title":"Cell-mediated immune response in experimental visceral leishmaniasis. 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