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In studies designed to ascertain the role of IFN-\u03b3 in<jats:italic>Leishmania amazonensis<\/jats:italic>infection, we were surprised to find that IFN-\u03b3 could promote<jats:italic>L. amazonensis<\/jats:italic>amastigote replication in macrophages (M\u03a6s), although it activated M\u03a6s to kill promastigotes. The replication-promoting effect of IFN-\u03b3 on amastigotes was independent of the source and genetic background of M\u03a6s, was apparently not affected by surface opsonization of amastigotes, was not mediated by interleukin-10 or transforming growth factor \u03b2, and was observed at different temperatures. Consistent with the different fates of promastigotes and amastigotes in IFN-\u03b3-stimulated M\u03a6s,<jats:italic>L. amazonensis<\/jats:italic>-specific Th1 transfer helped recipient mice control<jats:italic>L. amazonensis<\/jats:italic>infection established by promastigotes but not<jats:italic>L. amazonensis<\/jats:italic>infection established by amastigotes. On the other hand, IFN-\u03b3 could stimulate M\u03a6s to limit amastigote replication when it was coupled with lipopolysaccharides but not when it was coupled with tumor necrosis factor alpha. Thus, IFN-\u03b3 may play a bidirectional role at the level of parasite-M\u03a6 interactions; when it is optimally coupled with other factors, it has a protective effect against infection, and in the absence of such synergy it promotes amastigote growth. These results reveal a quite unexpected aspect of the<jats:italic>L. amazonensis<\/jats:italic>parasite and have important implications for understanding the pathogenesis of the disease and for developing vaccines and immunotherapies.<\/jats:p>","DOI":"10.1128\/iai.72.2.988-995.2004","type":"journal-article","created":{"date-parts":[[2004,1,24]],"date-time":"2004-01-24T23:46:23Z","timestamp":1074987983000},"page":"988-995","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":75,"title":["Enhanced Replication of<i>Leishmania amazonensis<\/i>Amastigotes in Gamma Interferon-Stimulated Murine Macrophages: Implications for the Pathogenesis of Cutaneous Leishmaniasis"],"prefix":"10.1128","volume":"72","author":[{"given":"Hai","family":"Qi","sequence":"first","affiliation":[{"name":"Department of Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxiang","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77555"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanchaya","family":"Wanasen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77555"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn","family":"Soong","sequence":"additional","affiliation":[{"name":"Department of Pathology"},{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77555"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.7.2952-2959.1993"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-308X(08)60022-6"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830260627"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.162.1.324"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2840015"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(98)00578-X"},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"4378","DOI":"10.4049\/jimmunol.153.10.4378","volume":"153","year":"1994","unstructured":"Chakkalath, H. 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