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

Olivia J. S. Macleod, Jean-Mathieu Bart, Paula MacGregor, Lori Peacock, Nicholas J. Savill, Svenja Hester, Sophie Ravel, Jack D. Sunter, Camilla Trevor, Steven Rust, Tristan J. Vaughan, Ralph Minter, Shabaz Mohammed, Wendy Gibson, Martin C. Taylor, Matthew K. Higgins () and Mark Carrington ()
Additional contact information
Olivia J. S. Macleod: University of Cambridge
Jean-Mathieu Bart: University of Montpellier
Paula MacGregor: University of Cambridge
Lori Peacock: University of Bristol
Nicholas J. Savill: University of Edinburgh
Svenja Hester: University of Oxford
Sophie Ravel: University of Montpellier
Jack D. Sunter: Oxford Brookes University
Camilla Trevor: University of Cambridge
Steven Rust: AstraZeneca R&D
Tristan J. Vaughan: AstraZeneca R&D
Ralph Minter: AstraZeneca R&D
Shabaz Mohammed: University of Oxford
Wendy Gibson: University of Bristol
Martin C. Taylor: London School of Hygiene and Tropical Medicine
Matthew K. Higgins: University of Oxford
Mark Carrington: University of Cambridge

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract 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.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-15125-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15125-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-15125-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().