{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T19:35:22Z","timestamp":1791056122666,"version":"4.1.0"},"reference-count":45,"publisher":"Rockefeller University Press","issue":"7","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,4,7]]},"abstract":"<jats:p>Despite permitting uncontrolled intracellular visceral infection for 8 wk, interferon-\u03b3 (IFN-\u03b3) gene knockout (GKO) mice infected with Leishmania donovani proceeded to reduce liver parasite burdens by 50% by week 12. This late-developing IFN-\u03b3\u2013independent antileishmanial mechanism appeared to be dependent largely on endogenous tumor necrosis factor-\u03b1 (TNF-\u03b1): L. donovani infection induced TNF-\u03b1 mRNA expression in parasitized GKO livers and neutralization of TNF-\u03b1 reversed control at week 12. 7 d of treatment of infected GKO mice with interleukin-12 (IL-12) readily induced leishmanicidal activity and also partially restored the near-absent tissue granulomatous response, observations that for the first time expand the antimicrobial repertoire of IL-12 to include IFN-\u03b3\u2013independent effects. The action of IL-12 against L. donovani was TNF-\u03b1 dependent and required the activity of inducible nitric oxide synthase. These results point to the presence of an IFN-\u03b3\u2013independent antimicrobial mechanism, mediated by TNF-\u03b1, which remains quiescent until activated late in the course of experimental visceral leishmaniasis. However, as judged by the effect of exogenous IL-12 this quiescent mechanism can readily be induced to rapidly yield enhanced intracellular antimicrobial activity.<\/jats:p>","DOI":"10.1084\/jem.185.7.1231","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:49:30Z","timestamp":1027702170000},"page":"1231-1240","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":117,"title":["Intracellular Antimicrobial Activity in the Absence of Interferon-\u03b3: Effect of Interleukin-12 in Experimental Visceral Leishmaniasis in Interferon-\u03b3 Gene-disrupted Mice"],"prefix":"10.1084","volume":"185","author":[{"given":"Alice P.","family":"Taylor","sequence":"first","affiliation":[{"name":"From the Department of Medicine, Cornell University Medical College, New York 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry W.","family":"Murray","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Cornell University Medical College, New York 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1997,4,7]]},"reference":[{"key":"2023072915323040700_B1","doi-asserted-by":"crossref","first-page":"4244","DOI":"10.4049\/jimmunol.143.12.4244","article-title":"Experimental visceral leishmaniasis: role of endogenous IFN-\u03b3 in host defense and tissue granulomatous response","volume":"143","author":"Squires","year":"1989","journal-title":"J Immunol"},{"key":"2023072915323040700_B2","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1093\/infdis\/161.5.992","article-title":"Effect of continuous administration of interferon-\u03b3 in experimental visceral leishmaniasis","volume":"161","author":"Murray","year":"1990","journal-title":"J Infect Dis"},{"key":"2023072915323040700_B3","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1126\/science.8456300","article-title":"Multiple defects of immune cell function in mice with disrupted interferon-\u03b3 genes","volume":"159","author":"Dalton","year":"1993","journal-title":"Science (Wash DC)"},{"key":"2023072915323040700_B4","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1084\/jem.178.5.1725","article-title":"Response to influenza infection in mice with a targeted disruption in the interferon-\u03b3 gene","volume":"178","author":"Graham","year":"1993","journal-title":"J Exp Med"},{"key":"2023072915323040700_B5","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1084\/jem.178.6.2243","article-title":"Disseminated tuberculosis in interferon-\u03b3 gene-disrupted mice","volume":"178","author":"Cooper. 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