Tetraspanin CD82 Organizes Dectin-1 into Signaling Domains to Mediate Cellular Responses to Candida albicans
| Autor: | Vinod Kumar, Jane B Jeffery, Sunnie G Kuna, Paige E. Negoro, Mihai G. Netea, Rebecca A Ward, Ethan C. Garner, Jenny M. Tam, Frank L. van de Veerdonk, Michael K. Mansour, François Le Naour, Cindy K. Miranti, Anna Sokolovska, Kara G. Lassen, Carl N. Wivagg, Nida S. Khan, Ramnik J. Xavier, Jatin M. Vyas, Richard A. Dutko, Jennifer L. Reedy, Mridu Acharya, Shuying Xu, Vasiliki Matzaraki, Michael Feldman, Daniel P Lukason |
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| Přispěvatelé: | Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI) |
| Rok vydání: | 2019 |
| Předmět: |
Phagocytic cup
medicine.medical_treatment Interleukin-1beta Immunology lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] Syk Kangai-1 Protein Polymorphism Single Nucleotide Article Cell Line Mice 03 medical and health sciences Membrane Microdomains 0302 clinical medicine All institutes and research themes of the Radboud University Medical Center Tetraspanin Phagosomes Candida albicans medicine Animals Humans Immunology and Allergy Genetic Predisposition to Disease Lectins C-Type Mice Knockout Immunity Cellular biology Tumor Necrosis Factor-alpha Macrophages Cell Membrane Candidiasis biology.organism_classification Corpus albicans Cell biology Mice Inbred C57BL Cytokine Membrane protein Signal transduction Signal Transduction 030215 immunology |
| Zdroj: | Journal of Immunology, 202(11), 3256-3266. AMER ASSOC IMMUNOLOGISTS Journal of Immunology, 202, 11, pp. 3256-3266 Journal of Immunology, 202, 3256-3266 J Immunol |
| ISSN: | 0022-1767 |
| DOI: | 10.4049/jimmunol.1801384 |
| Popis: | Tetraspanins are a family of proteins possessing four transmembrane domains that help in lateral organization of plasma membrane proteins. These proteins interact with each other as well as other receptors and signaling proteins, resulting in functional complexes called “tetraspanin microdomains.” Tetraspanins, including CD82, play an essential role in the pathogenesis of fungal infections. Dectin-1, a receptor for the fungal cell wall carbohydrate β-1,3-glucan, is vital to host defense against fungal infections. The current study identifies a novel association between tetraspanin CD82 and Dectin-1 on the plasma membrane of Candida albicans–containing phagosomes independent of phagocytic ability. Deletion of CD82 in mice resulted in diminished fungicidal activity, increased C. albicans viability within macrophages, and decreased cytokine production (TNF-α, IL-1β) at both mRNA and protein level in macrophages. Additionally, CD82 organized Dectin-1 clustering in the phagocytic cup. Deletion of CD82 modulates Dectin-1 signaling, resulting in a reduction of Src and Syk phosphorylation and reactive oxygen species production. CD82 knockout mice were more susceptible to C. albicans as compared with wild-type mice. Furthermore, patient C. albicans–induced cytokine production was influenced by two human CD82 single nucleotide polymorphisms, whereas an additional CD82 single nucleotide polymorphism increased the risk for candidemia independent of cytokine production. Together, these data demonstrate that CD82 organizes the proper assembly of Dectin-1 signaling machinery in response to C. albicans. |
| Databáze: | OpenAIRE |
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