| Leishmania donovani amastigotes impair gamma interferon-induced STAT1alpha nuclear translocation by blocking the interaction between STAT1alpha and importin-alpha5. | |
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MedLine Citation:
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PMID: 20566692 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The protozoan parasite Leishmania donovani, 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-gamma). Our knowledge of the strategies utilized by L. donovani to impair macrophage responsiveness to IFN-gamma remains fragmentary. In the present study, we investigated the impact of an infection by the amastigote stage of L. donovani on IFN-gamma 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-gamma-induced expression of major histocompatibility complex class II and inducible nitric oxide synthase (iNOS) were strongly reduced in L. donovani amastigote-infected macrophages. As the expression of those genes is mediated by the transcription factors STAT1alpha and IFN regulatory factor 1 (IRF-1), we investigated their activation in amastigote-infected macrophages treated with IFN-gamma. We found that whereas STAT1alpha 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 STAT1alpha, and further analyses revealed that the IFN-gamma-induced STAT1alpha association with the nuclear transport adaptor importin-alpha5 was compromised in L. donovani amastigote-infected macrophages. Taken together, our results provide evidence for a novel mechanism used by L. donovani amastigotes to interfere with IFN-gamma-activated macrophage functions and provide a better understanding of the strategies deployed by this parasite to ensure its intracellular survival. |
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Authors:
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Christine Matte; Albert Descoteaux |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-21 |
Journal Detail:
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Title: Infection and immunity Volume: 78 ISSN: 1098-5522 ISO Abbreviation: Infect. Immun. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-18 Completed Date: 2010-09-13 Revised Date: 2011-07-25 |
Medline Journal Info:
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Nlm Unique ID: 0246127 Medline TA: Infect Immun Country: United States |
Other Details:
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Languages: eng Pagination: 3736-43 Citation Subset: IM |
Affiliation:
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INRS-Institut Armand-Frappier, 531, Boul. des Prairies, Laval, QC, Canada H7V 1B7. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Active Transport, Cell Nucleus Animals Cell Nucleus / metabolism* Female Interferon Regulatory Factor-1 / genetics Interferon-Stimulated Gene Factor 3 / analysis, metabolism* Interferon-gamma / physiology* Leishmania donovani / physiology* Macrophage Activation* Mice Mice, Inbred BALB C Phosphorylation Signal Transduction alpha Karyopherins / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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MOP-12933//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Interferon Regulatory Factor-1; 0/Interferon-Stimulated Gene Factor 3; 0/KPNA1 protein, mouse; 0/alpha Karyopherins; 0/gamma interferon activation factor; 82115-62-6/Interferon-gamma |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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