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12:48
Purification of the Membrane Compartment for Endoplasmic Reticulum-associated Degradation of Exogenous Antigens in Cross-presentation
Published on: August 21, 2017
Carbohydrate oxidation acidifies endosomes, regulating antigen processing and TLR9 signaling
Colleen J Lewis1, Brian A Cobb
1Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|March 5, 2010
Summary
Oxidation of microbial carbohydrates by phagocytes enhances immune responses. This process promotes antigen processing for T cell recognition and activates Toll-like receptor 9 (TLR9) signaling, improving pathogen clearance.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Phagocytes eliminate encapsulated microbes via oxidative carbohydrate cleavage.
- Released microbial components act as immune signaling molecules.
- These components include glycan fragments, proteins, and nucleic acids.
Purpose of the Study:
- To investigate the role of NO-mediated oxidation in phagocyte-mediated immune responses.
- To elucidate the impact of carbohydrate oxidation on antigen processing and immune receptor signaling.
Main Methods:
- Confocal microscopy of live macrophages and dendritic cells.
- Analysis of vesicular acidification, T cell-dependent antigen cleavage, and Toll-like receptor 9 (TLR9) signaling.
Main Results:
- Carbohydrate endocytosis induced NO-mediated oxidative acidification.
- This acidification inhibited polysaccharide antigen cleavage but promoted protein antigen processing.
- CpG-mediated TLR9 signaling was facilitated by this oxidative process.
Conclusions:
- Oxidation of microbial carbohydrates is crucial for adaptive immunity.
- It enhances MHC class II presentation of protein antigens and DNA-based innate immunity via TLR9.
- This mechanism optimizes immune responses against encapsulated microbes.
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