title: Tsetse GmmSRPN10 has anti-complement activity and is important for successful establishment of trypanosome infections in the fly midgut.
abstract: The complement cascade in mammalian blood can damage the alimentary tract of haematophagous arthropods. As such, these animals have evolved their own repertoire of complement-inactivating factors, which are inadvertently exploited by blood-borne pathogens to escape complement lysis. Unlike the bloodstream stages, the procyclic (insect) stage of Trypanosoma brucei is highly susceptible to complement killing, which is puzzling considering that a tsetse takes a bloodmeal every 2-4 days. In this study, we identified four tsetse (Glossina morsitans morsitans) serine protease inhibitors (serpins) from a midgut expressed sequence tag (EST) library (GmmSRPN3, GmmSRPN5, GmmSRPN9 and GmmSRPN10) and investigated their role in modulating the establishment of a T. brucei infection in the midgut. Although not having evolved in a common blood-feeding ancestor, all four serpins have an active site sharing remarkable homology with the human complement C1-inhibitor serpin, SerpinG1. RNAi knockdown of individual GmmSRPN9 and GmmSRPN10 genes resulted in a significant decreased rate of infection by procyclic form T. brucei. Furthermore, recombinant GmmSRPN10 was both able to inhibit the activity of human complement-cascade serine proteases, C1s and Factor D, and to protect the in vitro killing of procyclic trypanosomes when incubated with complement-activated human serum. Thus, the secretion of serpins, which may be part of a bloodmeal complement inactivation system in tsetse, is used by procyclic trypanosomes to evade an influx of fresh trypanolytic complement with each bloodmeal. This highlights another facet of the complicated relationship between T. brucei and its tsetse vector, where the parasite takes advantage of tsetse physiology to further its chances of propagation and transmission.
authors.affiliation: Department of Life Sciences, Sir Alexander Fleming Building, Imperial College-South Kensington, London, United Kingdom; Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom, 3 Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Cher-Pheng
authors.initials: CP
authors.lastname: Ooi
authors.affiliation: Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom, 3 Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Lee R
authors.initials: LR
authors.lastname: Haines
authors.affiliation: Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom, 3 Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Southern
authors.affiliation: Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom, 3 Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lehane
authors.affiliation: Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom, 3 Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Acosta-Serrano
mesh_terms: D000818:Animals; D020224:Expressed Sequence Tags; D041981:Gastrointestinal Tract / Q000469:parasitology*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D015723:Gene Library; D006790:Host-Parasite Interactions; D019476:Insect Proteins / Q000378:metabolism*; D010802:Phylogeny; D012330:RNA, Double-Stranded; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015843:Serpins / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000502:physiology*; D014370:Tsetse Flies / Q000469:parasitology*
chemical_list: D019476:Insect Proteins; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D015843:Serpins