Invariant surface glycoprotein 65 of Trypanosoma brucei is a complement C3 receptor.

Autor: Macleod OJS; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK., Cook AD; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK., Webb H; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK., Crow M; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK., Burns R; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK., Redpath M; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK., Seisenberger S; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK., Trevor CE; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK., Peacock L; Bristol Veterinary School and School of Biological Sciences, University of Bristol, Bristol, UK., Schwede A; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK., Kimblin N; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK., Francisco AF; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK., Pepperl J; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK., Rust S; Antibody Discovery and Protein Engineering, Biopharmaceuticals R&D, AstraZeneca, Cambridge, UK., Voorheis P; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland., Gibson W; Bristol Veterinary School and School of Biological Sciences, University of Bristol, Bristol, UK., Taylor MC; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK., Higgins MK; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK. matthew.higgins@bioch.ox.ac.uk.; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK. matthew.higgins@bioch.ox.ac.uk., Carrington M; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK. mc115@cam.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Aug 29; Vol. 13 (1), pp. 5085. Date of Electronic Publication: 2022 Aug 29.
DOI: 10.1038/s41467-022-32728-9
Abstrakt: African trypanosomes are extracellular pathogens of mammals and are exposed to the adaptive and innate immune systems. Trypanosomes evade the adaptive immune response through antigenic variation, but little is known about how they interact with components of the innate immune response, including complement. Here we demonstrate that an invariant surface glycoprotein, ISG65, is a receptor for complement component 3 (C3). We show how ISG65 binds to the thioester domain of C3b. We also show that C3 contributes to control of trypanosomes during early infection in a mouse model and provide evidence that ISG65 is involved in reducing trypanosome susceptibility to C3-mediated clearance. Deposition of C3b on pathogen surfaces, such as trypanosomes, is a central point in activation of the complement system. In ISG65, trypanosomes have evolved a C3 receptor which diminishes the downstream effects of C3 deposition on the control of infection.
(© 2022. The Author(s).)
Databáze: MEDLINE
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