Document Detail


Carbohydrate oxidation acidifies endosomes, regulating antigen processing and TLR9 signaling.
MedLine Citation:
PMID:  20200279     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Phagocytes kill encapsulated microbes through oxidative cleavage of surface carbohydrates, releasing glycan fragments and microbial contents that serve as ligands for immune receptors, which tailor the immune response against the offending pathogen. The glycan fragments serve as MHC class II (MHC II) ligands and innate receptor agonists, whereas microbial proteins serve as substrates for proteolytic cleavage and MHC II presentation, and released nucleic acids activate innate pattern-recognition receptors (e.g., TLR9). In the current study, confocal microscopy of live macrophages and dendritic cells revealed that endocytosis of carbohydrates lead to vesicular acidification independent of proton pump activity. Acidification was dependent on NO-mediated oxidation in the presence of the ingested carbohydrate and was sufficient to negatively regulate T cell-dependent polysaccharide Ag cleavage, promote acid-dependent protein Ag processing, and facilitate CpG-mediated TLR9 signaling. Our findings lead to a model in which oxidation of carbohydrates from encapsulated microbes facilitates adaptive immune responses against microbial protein and carbohydrate Ags through promoting Ag processing for MHC II-mediated presentation as well as innate responses against released microbial DNA via TLR9 signaling.
Authors:
Colleen J Lewis; Brian A Cobb
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-03-03
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  184     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-22     Completed Date:  2010-04-27     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3789-800     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adaptive Immunity / immunology
Animals
Antigen Presentation / physiology*
Antigen-Presenting Cells / immunology,  metabolism
Antigens, Bacterial / chemistry,  immunology,  metabolism*
Bacterial Capsules / chemistry,  immunology,  metabolism
Carbohydrate Metabolism / immunology*
Cell Separation
DNA, Bacterial / immunology
Dendritic Cells / immunology,  metabolism
Endosomes / immunology,  metabolism*
Flow Cytometry
Hydrogen-Ion Concentration
Macrophages / immunology,  metabolism
Mice
Mice, Inbred C57BL
Microscopy, Confocal
Nitric Oxide / immunology,  metabolism
Oxidation-Reduction
Signal Transduction / immunology*
Toll-Like Receptor 9 / immunology,  metabolism*
Grant Support
ID/Acronym/Agency:
AI062707/AI/NIAID NIH HHS; DP2 OD004225/OD/NIH HHS; DP2 OD004225-01/OD/NIH HHS; K22 AI062707/AI/NIAID NIH HHS; K22 AI062707-02/AI/NIAID NIH HHS; OD004225/OD/NIH HHS; R01 GM082916/GM/NIGMS NIH HHS; R01 GM082916-01A2/GM/NIGMS NIH HHS; R21 AI079756/AI/NIAID NIH HHS; R21 AI079756-02/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, Bacterial; 0/DNA, Bacterial; 0/Toll-Like Receptor 9; 31C4KY9ESH/Nitric Oxide
Comments/Corrections

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