A receptor for the complement regulator factor H increases transmission of trypanosomes to tsetse flies.
Animals
Antibodies, Monoclonal
/ metabolism
CHO Cells
Cattle
Cell Membrane
/ metabolism
Complement C3b
/ metabolism
Complement Factor H
/ chemistry
Cricetinae
Cricetulus
Mice, Inbred BALB C
Parasitemia
/ blood
Protein Binding
Protein Domains
Protozoan Proteins
/ chemistry
Receptors, Cell Surface
/ metabolism
Trypanosoma
/ physiology
Tsetse Flies
/ parasitology
Up-Regulation
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
12 03 2020
12 03 2020
Historique:
received:
21
06
2019
accepted:
15
02
2020
entrez:
14
3
2020
pubmed:
14
3
2020
medline:
7
7
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32165615
doi: 10.1038/s41467-020-15125-y
pii: 10.1038/s41467-020-15125-y
pmc: PMC7067766
doi:
Substances chimiques
Antibodies, Monoclonal
0
Protozoan Proteins
0
Receptors, Cell Surface
0
Complement C3b
80295-43-8
Complement Factor H
80295-65-4
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1326Subventions
Organisme : Medical Research Council
ID : MR/P001424/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M008924/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 217138/Z/19/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 101020/Z/13/Z
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : P50 GM073197
Pays : United States
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