| Involvement of glycoreceptors in galactoxylomannan-induced T cell death. | |
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MedLine Citation:
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PMID: 19414751 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The major virulence factor of Cryptococcus neoformans is its capsular polysaccharide, which is also released into tissues. The shed polysaccharide is composed of glucuronoxylomannan, galactoxylomannan (GalXM), and mannoproteins. In a previous study, we demonstrated a direct interaction of purified soluble GalXM with T cells that induced their apoptosis. In this study, we focus on the mechanisms involved in the apoptotic effect of GalXM. In our experimental system, we analyzed the effect of GalXM on purified human T cells and Jurkat cells, a T cell line routinely used for apoptotic studies. Our results reveal that GalXM activates the extrinsic and intrinsic apoptotic pathways through the cleavage and recruitment of caspase-8. Caspase-8 elicits the downstream executioner caspase-3, caspase-6, and caspase-7 both directly and indirectly, via Bid cleavage and caspase-9 activation. These effects appeared to be primarily mediated by the interaction of GalXM with the glycoreceptors, which differed in human T and Jurkat cells. CD45 was primarily involved in Jurkat cells apoptosis while CD7 and CD43 mediated human T cell apoptosis. Our results highlight a new mechanism by which a microbial product can contribute to virulence through direct interaction with T cell glycoreceptors, thereby triggering lymphocyte apoptosis. |
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Authors:
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Eva Pericolini; Elena Gabrielli; Elio Cenci; Magdia De Jesus; Francesco Bistoni; Arturo Casadevall; Anna Vecchiarelli |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 182 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2009 May |
Date Detail:
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Created Date: 2009-05-05 Completed Date: 2009-05-26 Revised Date: 2010-09-27 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 6003-10 Citation Subset: AIM; IM |
Affiliation:
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Department of Experimental Medicine and Biochemical Sciences, Microbiology Section, University of Perugia, Perugia, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, CD43
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immunology,
metabolism* Antigens, CD45 / immunology, metabolism* Antigens, CD7 / immunology, metabolism* Apoptosis / immunology* Blotting, Western Caspase 3 / immunology, metabolism Caspase 6 / immunology, metabolism Caspase 7 / immunology, metabolism Cryptococcus neoformans / immunology Enzyme Activation / immunology Flow Cytometry Humans Immunoblotting Jurkat Cells Polysaccharides, Bacterial / immunology* T-Lymphocytes / immunology, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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AI14209/AI/NIAID NIH HHS; R01 AI033774-16/AI/NIAID NIH HHS; R01AI033774-15/AI/NIAID NIH HHS; R01HL059842-12/HL/NHLBI NIH HHS; R37AI033142/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD43; 0/Antigens, CD7; 0/Polysaccharides, Bacterial; 70903-49-0/galactoxylomannan; EC 3.1.3.48/Antigens, CD45; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 6; EC 3.4.22.-/Caspase 7 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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