1. A receptor for the complement regulator factor H increases transmission of trypanosomes to tsetse flies
- Author
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Lori Peacock, Olivia J. S. Macleod, Jean-Mathieu Bart, Sophie Ravel, Svenja Hester, Martin C. Taylor, Camilla Trevor, Ralph Minter, Jack D. Sunter, Tristan J. Vaughan, Wendy Gibson, Paula MacGregor, Steven Rust, Matthew K. Higgins, Shabaz Mohammed, Mark Carrington, Nicholas J. Savill, Interactions hôtes-vecteurs-parasites-environnement dans les maladies tropicales négligées dues aux trypanosomatides (UMR INTERTRYP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université de Bordeaux (UB), Macleod, Olivia J S [0000-0002-5747-8019], Bart, Jean-Mathieu [0000-0001-5707-3778], MacGregor, Paula [0000-0003-0919-3745], Savill, Nicholas J [0000-0002-9769-6168], Sunter, Jack D [0000-0002-2836-9622], Minter, Ralph [0000-0001-5571-3102], Mohammed, Shabaz [0000-0003-2640-9560], Taylor, Martin C [0000-0003-4147-0693], Higgins, Matthew K [0000-0002-2870-1955], Carrington, Mark [0000-0002-6435-7266], Apollo - University of Cambridge Repository, Macleod, Olivia JS [0000-0002-5747-8019], Macleod, Olivia J. S. [0000-0002-5747-8019], Savill, Nicholas J. [0000-0002-9769-6168], Sunter, Jack D. [0000-0002-2836-9622], Taylor, Martin C. [0000-0003-4147-0693], and Higgins, Matthew K. [0000-0002-2870-1955]
- Subjects
0301 basic medicine ,Chemistry(all) ,Receptor expression ,Protozoan Proteins ,Regulator ,General Physics and Astronomy ,13 ,Parasitemia ,14 ,Cricetinae ,Parasite immune evasion ,AFRIQUE SUBSAHARIENNE ,Receptor ,lcsh:Science ,64 ,Mice, Inbred BALB C ,Multidisciplinary ,biology ,article ,Antibodies, Monoclonal ,Up-Regulation ,Cell biology ,3. Good health ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,Complement Factor H ,Factor H ,Complement C3b ,Pathogens ,Protein Binding ,Trypanosoma ,Tsetse Flies ,101 ,145 ,Science ,030106 microbiology ,parasite host response ,101/58 ,Receptors, Cell Surface ,CHO Cells ,Physics and Astronomy(all) ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Cricetulus ,Immune system ,Protein Domains ,82/103 ,Animals ,631/326/417/2547 ,631/326/417/2546 ,82/83 ,x-ray crystallography ,X-ray crystallography ,631/326/421 ,Biochemistry, Genetics and Molecular Biology(all) ,Cell Membrane ,fungi ,Tsetse fly ,pathogens ,General Chemistry ,biology.organism_classification ,030104 developmental biology ,631/535/1266 ,Alternative complement pathway ,Cattle ,lcsh:Q ,parasite immune evasion ,119 ,631/45/535/1266 ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Parasite host response - 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., African trypanosome infections can persist for years, but immune evasion mechanisms are not fully understood. Here, Macleod et al. identify a trypanosome receptor for mammalian factor H, a negative regulator of the alternative complement pathway, that increases parasite transmission to tsetse flies.
- Published
- 2020
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