| Pathogen-Derived Oligosaccharides Improve Innate Immune Response to Intracellular Parasite Infection. | |
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MedLine Citation:
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PMID: 21763266 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Pathogen glycolipids, including Leishmania spp. lipophosphoglycan (LPG) and Mycobacterium tuberculosis mannosylated lipoarabinomannan (ManLAM), modulate essential interactions with host phagocytic cells. Polysaccharide and lipid components promote immunomodulation. Owing to the stereochemistry required to synthesize oligosaccharides, the roles for oligosaccharides in the pathogenesis of infectious diseases have remained largely unknown. Recent advances in carbohydrate chemistry allowed us to synthesize pathogen surface oligosaccharides to discern their immune response-altering activities. Trimannose cap carbohydrates from ManLAM and LPG altered the production of proinflammatory cytokines via a toll-like receptor (TLR2)-mediated mechanism in vitro and in vivo. In vivo treatment with trimannose led to increased Th1-polarizing, IL-12p40-producing cells from the draining lymph nodes of treated Leishmania major-infected mice compared with cells from untreated infected mice. Trimannose treatment increased the production of other Th1 proinflammatory cytokines (ie, interferon-γ, IL-6, and tumor necrosis factor-α) critical for a productive immune response to either pathogen. This significant difference in cytokine production between trimannose cap sugar-treated and control groups was not observed in draining lymph node cells from TLR2(-/-) mice. Type of inflammation and rate of bead entry into macrophages and dendritic cells were different for trimannose-coated beads compared with control oligosaccharide-coated beads, indicating selective lectin receptor/oligosaccharide interactions mediating cell entry and cytokine production. These novel findings may prompt the development of targeted oligosaccharide adjuvants against chronic infections. |
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Authors:
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Alex Osanya; Eun-Ho Song; Kyle Metz; Raeann M Shimak; Paola Mercedes Boggiatto; Elise Huffman; Charles Johnson; Jesse M Hostetter; Nicola L B Pohl; Christine A Petersen |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-13 |
Journal Detail:
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Title: The American journal of pathology Volume: - ISSN: 1525-2191 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-7-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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