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A receptor for the complement regulator factor H increases transmission of trypanosomes to tsetse flies

Title: A receptor for the complement regulator factor H increases transmission of trypanosomes to tsetse flies
Authors: Macleod, Olivia J. S.; Bart, Jean-Mathieu; Macgregor, Paula; Peacock, Lori; Hester, Svenja; Ravel, Sophie; Sunter, Jack D.; Trevor, Camilla; Rust, Steven; Vaughan, Tristan J.; Minter, Ralph; Mohammed, Shabaz; Gibson, Wendy; Taylor, Martin C.; Higgins, Matthew K.; Carrington, Mark
Source: Macleod, O J S, Bart, J-M, Macgregor, P, Peacock, L, Hester, S, Ravel, S, Sunter, J D, Trevor, C, Rust, S, Vaughan, T J, Minter, R, Mohammed, S, Gibson, W, Taylor, M C, Higgins, M K & Carrington, M 2020, 'A receptor for the complement regulator factor H increases transmission of trypanosomes to tsetse flies', Nature Communications, vol. 11, 1326 (2020). https://doi.org/10.1038/s41467-020-15125-y
Publication Year: 2020
Collection: University of Bristol: Bristol Reserach
Subject Terms: parasite host response; parasite immune evasion; pathogens; x-ray crystallography
Description: Persistent pathogens have evolved to avoid elimination by the mammalian immune system including mechanisms to evade complement. Infections with African trypanosomes can persist for years and cause human and animal disease throughout sub-Saharan Africa. It is not known how trypanosomes limit the action of the alternative complement pathway. Here we identify an African trypanosome receptor for mammalian factor H, a negative regulator of the alternative pathway. Structural studies show how the receptor binds ligand, leaving inhibitory domains of factor H free to inactivate complement C3b deposited on the trypanosome surface. Receptor expression is highest in developmental stages transmitted to the tsetse fly vector and those exposed to blood meals in the tsetse gut. Receptor gene deletion reduced tsetse infection, identifying this receptor as a virulence factor for transmission. This demonstrates how a pathogen evolved a molecular mechanism to increase transmission to an insect vector by exploitation of a mammalian complement regulator.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/32165615; info:eu-repo/semantics/altIdentifier/hdl/https://hdl.handle.net/1983/c5c53da7-3964-4ea9-9272-6b35f247c58f
DOI: 10.1038/s41467-020-15125-y
Availability: https://hdl.handle.net/1983/c5c53da7-3964-4ea9-9272-6b35f247c58f; https://research-information.bris.ac.uk/en/publications/c5c53da7-3964-4ea9-9272-6b35f247c58f; https://doi.org/10.1038/s41467-020-15125-y; https://research-information.bris.ac.uk/ws/files/230702048/s41467_020_15125_y.pdf
Rights: info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.DF9548EF
Database: BASE