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

DOI: 10.1038/s41467-020-15125-y DOI Help

Authors: Olivia J. S. Macleod (University of Cambridge) , Jean-Mathieu Bart (Intertryp, IRD, Cirad, 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 (Intertryp, IRD, Cirad, University of Montpellier) , Jack D. Sunter (Oxford Brookes University) , Camilla Trevor (University of Cambridge; AstraZeneca R&D) , 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 Higgins (University of Oxford) , Mark Carrington (University of Cambridge)
Co-authored by industrial partner: Yes

Type: Journal Paper
Journal: Nature Communications , VOL 11

State: Published (Approved)
Published: March 2020
Diamond Proposal Number(s): 18069

Open Access Open Access

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.

Journal Keywords: Parasite host response; Parasite immune evasion; Pathogens; X-ray crystallography

Diamond Keywords: Sleeping Sickness

Subject Areas: Biology and Bio-materials

Instruments: I03-Macromolecular Crystallography

Added On: 25/03/2020 10:52


Discipline Tags:

Pathogens Infectious Diseases Disease in the Developing World Health & Wellbeing Structural biology Life Sciences & Biotech Parasitology

Technical Tags:

Diffraction Macromolecular Crystallography (MX)