دورية أكاديمية
أعرض في EDS

The C-Type Lectin Receptor Dectin-2 Is a Receptor for Aspergillus fumigatus Galactomannan.

التفاصيل البيبلوغرافية
العنوان: The C-Type Lectin Receptor Dectin-2 Is a Receptor for Aspergillus fumigatus Galactomannan.
المؤلفون: Reedy JL; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Department of Medicine, Boston, Massachusetts, USA., Crossen AJ; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA., Negoro PE; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA., Harding HB; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA., Ward RA; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA., Vargas-Blanco DA; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA., Timmer KD; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA., Reardon CM; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA., Basham KJ; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA., Mansour MK; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Department of Medicine, Boston, Massachusetts, USA., Wüthrich M; Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, Wisconsin, USA., Fontaine T; Institut Pasteur, Université de Paris, INRAE, USC2019, Unité Biologie et Pathogénicité Fongiques, Paris, France., Latgé JP; Institute of Molecular Biology and Biotechnology (IMBBFORTH), University of Crete, Heraklion, Greece., Vyas JM; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Department of Medicine, Boston, Massachusetts, USA.
المصدر: MBio [mBio] 2023 Feb 28; Vol. 14 (1), pp. e0318422. Date of Electronic Publication: 2023 Jan 04.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Society for Microbiology
مواضيع طبية MeSH: Aspergillus fumigatus* , Mannans*, Animals ; Mice ; Humans ; Lectins, C-Type/metabolism ; Mammals/metabolism
مستخلص: Aspergillus fumigatus is a ubiquitous environmental mold that causes significant mortality particularly among immunocompromised patients. The detection of the Aspergillus -derived carbohydrate galactomannan in patient serum and bronchoalveolar lavage fluid is the major biomarker used to detect A. fumigatus infection in clinical medicine. Despite the clinical relevance of this carbohydrate, we lack a fundamental understanding of how galactomannan is recognized by the immune system and its consequences. Galactomannan is composed of a linear mannan backbone with galactofuranose sidechains and is found both attached to the cell surface of Aspergillus and as a soluble carbohydrate in the extracellular milieu. In this study, we utilized fungal-like particles composed of highly purified Aspergillus galactomannan to identify a C-type lectin host receptor for this fungal carbohydrate. We identified a novel and specific interaction between Aspergillus galactomannan and the C-type lectin receptor Dectin-2. We demonstrate that galactomannan bound to Dectin-2 and induced Dectin-2-dependent signaling, including activation of spleen tyrosine kinase, gene transcription, and tumor necrosis factor alpha (TNF-α) production. Deficiency of Dectin-2 increased immune cell recruitment to the lungs but was dispensable for survival in a mouse model of pulmonary aspergillosis. Our results identify a novel interaction between galactomannan and Dectin-2 and demonstrate that Dectin-2 is a receptor for galactomannan, which leads to a proinflammatory immune response in the lung. IMPORTANCE Aspergillus fumigatus is a fungal pathogen that causes serious and often fatal disease in humans. The surface of Aspergillus is composed of complex sugar molecules. Recognition of these carbohydrates by immune cells by carbohydrate lectin receptors can lead to clearance of the infection or, in some cases, benefit the fungus by dampening the host response. Galactomannan is a carbohydrate that is part of the cell surface of Aspergillus but is also released during infection and is found in patient lungs as well as their bloodstreams. The significance of our research is that we have identified Dectin-2 as a mammalian immune cell receptor that recognizes, binds, and signals in response to galactomannan. These results enhance our understanding of how this carbohydrate interacts with the immune system at the site of infection and will lead to broader understanding of how release of galactomannan by Aspergillus effects the immune response in infected patients.
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معلومات مُعتمدة: KL2 TR001100 United States TR NCATS NIH HHS; K08 AI141755 United States AI NIAID NIH HHS; R01 AI136529 United States AI NIAID NIH HHS; R01 AI150181 United States AI NIAID NIH HHS; R21 AI152499 United States AI NIAID NIH HHS
فهرسة مساهمة: Keywords: Aspergillus fumigatus; fungi; host-pathogen interactions; immune mechanisms; innate immunity; mycology
المشرفين على المادة: 11078-30-1 (galactomannan)
0 (Mannans)
0 (dectin-2, mouse)
0 (Lectins, C-Type)
تواريخ الأحداث: Date Created: 20230104 Date Completed: 20230302 Latest Revision: 20230926
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC9973300
DOI: 10.1128/mbio.03184-22
PMID: 36598192
قاعدة البيانات: MEDLINE
الوصف
تدمد:2150-7511
DOI:10.1128/mbio.03184-22