Dectin-1-triggered Recruitment of Light Chain 3 Protein to Phagosomes Facilitates Major Histocompatibility Complex Class II Presentation of Fungal-derived Antigens
| Autor: | Jun Ma, David M. Underhill, Courtney A. Becker, Clifford A. Lowell |
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| Rok vydání: | 2012 |
| Předmět: |
CD4-Positive T-Lymphocytes
beta-Glucans animal diseases Medical and Health Sciences Biochemistry Autophagy-Related Protein 5 Mice Phagosomes Lectins Phagosome Mice Knockout Antigen Presentation NADPH oxidase C-Type Intracellular Signaling Peptides and Proteins Pattern recognition receptor Protein-Tyrosine Kinases Biological Sciences Cell biology Fungal Infectious Diseases Microtubule-Associated Proteins Protein Binding Biochemistry & Molecular Biology Antigens Fungal Knockout Immunology Antigen presentation ATG5 chemical and pharmacologic phenomena Bone Marrow Cells Biology Cell Line Immune system Animals Syk Kinase Lectins C-Type Antigens Molecular Biology Innate immune system Macrophages Inflammatory and immune system Autophagy Histocompatibility Antigens Class II NADPH Oxidases Dendritic Cells Cell Biology biochemical phenomena metabolism and nutrition Enzyme Activation Emerging Infectious Diseases Chemical Sciences biology.protein bacteria |
| Zdroj: | The Journal of biological chemistry, vol 287, iss 41 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m112.382812 |
| Popis: | Dectin-1 is a pattern recognition receptor that is important for innate immune responses against fungi in humans and mice. Dectin-1 binds to β-glucans in fungal cell walls and triggers phagocytosis, production of reactive oxygen by the NADPH oxidase, and inflammatory cytokine production which all contribute to host immune responses against fungi. Although the autophagy pathway was originally characterized for its role in the formation of double-membrane compartments engulfing cytosolic organelles and debris, recent studies have suggested that components of the autophagy pathway may also participate in traditional phagocytosis. In this study, we show that Dectin-1 signaling in macrophages and bone marrow-derived dendritic cells triggers formation of LC3II, a major component of the autophagy machinery. Further, Dectin-1 directs the recruitment of LC3II to phagosomes, and this requires Syk, activation of reactive oxygen production by the NADPH oxidase, and ATG5. Using LC3-deficient dendritic cells we show that whereas LC3 recruitment to phagosomes is not important for triggering phagocytosis, killing or Dectin-1-mediated inflammatory cytokine production, it facilitates recruitment of MHC class II molecules to phagosomes and promotes presentation of fungal-derived antigens to CD4 T cells. |
| Databáze: | OpenAIRE |
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