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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 publication




Journal article


Nat Commun

Publication Date





Animals, Antibodies, Monoclonal, CHO Cells, Cattle, Cell Membrane, Complement C3b, Complement Factor H, Cricetinae, Cricetulus, Mice, Inbred BALB C, Parasitemia, Protein Binding, Protein Domains, Protozoan Proteins, Receptors, Cell Surface, Trypanosoma, Tsetse Flies, Up-Regulation