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Instruments / Technical Area	Publication Details	Published	Actions
I03-Macromolecular Crystallography	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 Higgins , Mark Carrington Nature Communications 11 DOI: 10.1038/s41467-020-15125-y Diamond Proposal Number(s): [18069] Open Access Show 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.	Mar 2020

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I03-Macromolecular Crystallography

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