| Comparative study of the ability of Leishmania mexicana promastigotes and amastigotes to alter macrophage signaling and functions. | |
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MedLine Citation:
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PMID: 20368344 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Leishmania alternates between two morphologically different stages, promastigotes and amastigotes. While the majority of reports focused on how the promastigote form can alter macrophage (Mphi) signaling and function, fewer reports investigated signaling alterations mediated by amastigotes, and there is a lack of comparative studies. In this study, we performed a comparison between the ability of both forms of the parasite to alter Mphi signaling and functions. Here, we show that both promastigotes and amastigotes were able to rapidly activate host protein tyrosine phosphatases (PTPs), importantly the Src homology 2 domain-containing PTP (SHP-1). However, we found that PTP-1B is specifically activated by promastigote but not amastigote infection and that lmcpb(-/-) promastigotes were no longer able to activate PTP-1B. We also show a similarity in the way promastigotes and amastigotes inactivate the transcription factors (TFs) STAT-1alpha and AP-1, but we show differences in the modulation of NF-kappaB, with promastigotes cleaving the p65 subunit, generating a smaller p35 subunit, and amastigotes fully degrading the p65 subunit with no p35 production. Importantly, we show that the cysteine proteinase LmCPb plays a key role in the alteration of NF-kappaB, STAT-1alpha, and AP-1 by promastigote and amastigote infections, ultimately leading to the inability of these TFs to translocate to the nucleus in response to gamma interferon (IFN-gamma) stimulation and thus contributing to the ability of both parasite forms to effectively block IFN-gamma-mediated nitric oxide (NO) production in Mphis. |
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Authors:
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Issa Abu-Dayyeh; Kasra Hassani; Edze R Westra; Jeremy C Mottram; Martin Olivier |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-05 |
Journal Detail:
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Title: Infection and immunity Volume: 78 ISSN: 1098-5522 ISO Abbreviation: Infect. Immun. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-20 Completed Date: 2010-06-01 Revised Date: 2011-03-03 |
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: 2438-45 Citation Subset: IM |
Affiliation:
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Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line Cysteine Proteases / metabolism Humans Interferon-Stimulated Gene Factor 3 / antagonists & inhibitors Interferon-gamma / immunology Leishmania mexicana / immunology*, pathogenicity* Macrophages / immunology*, parasitology* Mice Nitric Oxide / immunology Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism Protozoan Proteins / metabolism Signal Transduction* Transcription Factor AP-1 / antagonists & inhibitors Transcription Factor RelA / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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WT 079356//Wellcome Trust; //Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Interferon-Stimulated Gene Factor 3; 0/Protozoan Proteins; 0/Transcription Factor AP-1; 0/Transcription Factor RelA; 0/gamma interferon activation factor; 10102-43-9/Nitric Oxide; 82115-62-6/Interferon-gamma; EC 3.1.3.48/Protein Tyrosine Phosphatase, Non-Receptor Type 6; EC 3.4.-/Cysteine Proteases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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