Journal article
Pathogen-derived oligosaccharides improve innate immune response to intracellular parasite infection
The American journal of pathology, Vol.179(3), pp.1329-1337
09/2011
DOI: 10.1016/j.ajpath.2011.05.053
PMCID: PMC3157181
PMID: 21763266
Abstract
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.
Details
- Title: Subtitle
- Pathogen-derived oligosaccharides improve innate immune response to intracellular parasite infection
- Creators
- Alex Osanya - Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USAEun-Ho SongKyle MetzRaeann M ShimakPaola Mercedes BoggiattoElise HuffmanCharles JohnsonJesse M HostetterNicola L B PohlChristine A Petersen
- Resource Type
- Journal article
- Publication Details
- The American journal of pathology, Vol.179(3), pp.1329-1337
- DOI
- 10.1016/j.ajpath.2011.05.053
- PMID
- 21763266
- PMCID
- PMC3157181
- NLM abbreviation
- Am J Pathol
- ISSN
- 1525-2191
- eISSN
- 1525-2191
- Publisher
- United States
- Grant note
- R21AI074711 / NIAID NIH HHS R21 AI074711 / NIAID NIH HHS
- Language
- English
- Date published
- 09/2011
- Academic Unit
- Epidemiology; Internal Medicine
- Record Identifier
- 9983995025602771
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