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

Autor: 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
Přispěvatelé: 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], Higgins, Matthew K. [0000-0002-2870-1955]
Jazyk: angličtina
Rok vydání: 2020
Předmět:
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
Zdroj: Nature Communications, Vol 11, Iss 1, Pp 1-12 (2020)
Macleod, O J S, Bart, J M, MacGregor, P, Peacock, L, Savill, N J, 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, vol. 11, no. 1, 1326 . https://doi.org/10.1038/s41467-020-15125-y
Nature Communications
Nature Communications, Nature Publishing Group, 2020, 11, art. 1326 [12 p.]. ⟨10.1038/s41467-020-15125-y⟩
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, vol. 11, 1326 (2020) . https://doi.org/10.1038/s41467-020-15125-y
ISSN: 2041-1723
DOI: 10.1038/s41467-020-15125-y
Popis: 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.
Databáze: OpenAIRE
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