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, 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, Mark Carrington

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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.
Original languageEnglish
Article number1326 (2020)
Number of pages12
JournalNature Communications
Volume11
DOIs
Publication statusPublished - 12 Mar 2020

Keywords

  • parasite host response
  • parasite immune evasion
  • pathogens
  • x-ray crystallography

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    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, 11, [1326 (2020)]. https://doi.org/10.1038/s41467-020-15125-y