{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T11:54:29Z","timestamp":1789818869290,"version":"4.0.1"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2010,9,1]],"date-time":"2010-09-01T00:00:00Z","timestamp":1283299200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2010,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The protozoan parasite<jats:italic>Leishmania donovani<\/jats:italic>, the etiological agent of visceral leishmaniasis, is renowned for its capacity to sabotage macrophage functions and signaling pathways stimulated by activators such as gamma interferon (IFN-\u03b3). Our knowledge of the strategies utilized by<jats:italic>L. donovani<\/jats:italic>to impair macrophage responsiveness to IFN-\u03b3 remains fragmentary. In the present study, we investigated the impact of an infection by the amastigote stage of<jats:italic>L. donovani<\/jats:italic>on IFN-\u03b3 responses and signaling via the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in mouse bone marrow-derived macrophages. The levels of IFN-\u03b3-induced expression of major histocompatibility complex class II and inducible nitric oxide synthase (iNOS) were strongly reduced in<jats:italic>L. donovani<\/jats:italic>amastigote-infected macrophages. As the expression of those genes is mediated by the transcription factors STAT1\u03b1 and IFN regulatory factor 1 (IRF-1), we investigated their activation in amastigote-infected macrophages treated with IFN-\u03b3. We found that whereas STAT1\u03b1 protein levels and the levels of phosphorylation on Tyr701 and Ser727 were normal, IRF-1 expression was inhibited in infected macrophages. This inhibition of IRF-1 expression correlated with a defective nuclear translocation of STAT1\u03b1, and further analyses revealed that the IFN-\u03b3-induced STAT1\u03b1 association with the nuclear transport adaptor importin-\u03b15 was compromised in<jats:italic>L. donovani<\/jats:italic>amastigote-infected macrophages. Taken together, our results provide evidence for a novel mechanism used by<jats:italic>L. donovani<\/jats:italic>amastigotes to interfere with IFN-\u03b3-activated macrophage functions and provide a better understanding of the strategies deployed by this parasite to ensure its intracellular survival.<\/jats:p>","DOI":"10.1128\/iai.00046-10","type":"journal-article","created":{"date-parts":[[2010,6,22]],"date-time":"2010-06-22T02:00:21Z","timestamp":1277172021000},"page":"3736-3743","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":55,"title":["<i>Leishmania donovani<\/i>Amastigotes Impair Gamma Interferon-Induced STAT1\u03b1 Nuclear Translocation by Blocking the Interaction between STAT1\u03b1 and Importin-\u03b15"],"prefix":"10.1128","volume":"78","author":[{"given":"Christine","family":"Matte","sequence":"first","affiliation":[{"name":"INRS-Institut Armand-Frappier and Centre for Host-Parasite Interactions, Laval, QC, Canada H7V 1B7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Descoteaux","sequence":"additional","affiliation":[{"name":"INRS-Institut Armand-Frappier and Centre for Host-Parasite Interactions, Laval, QC, Canada H7V 1B7"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00812-09"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2008.02.019"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.4.2095-2101.2003"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2004.10.018"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199911)29:11<3737::AID-IMMU3737>3.0.CO;2-S"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(97)80166-5"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203481"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.9.11.5223-5227.1989"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00277-07"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M700464-JLR200"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M414126200"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00853-05"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01012-07"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1017996609928"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.8.4187"},{"key":"e_1_3_2_17_2","first-page":"ra58","volume":"2","year":"2009","unstructured":"Gomez, M. 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