Date Published: January 8, 2015
Publisher: Public Library of Science
Author(s): Cher-Pheng Ooi, Lee R. Haines, Daniel M. Southern, Michael J. Lehane, Alvaro Acosta-Serrano, José M. C. Ribeiro. http://doi.org/10.1371/journal.pntd.0003448
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.
Partial Text: Mammalian blood constitutes a challenging source of nutrition, yet a multitude of arthropods have evolved to exploit this survival niche . Besides developing physical and behavioural adaptations to evade their hosts, haematophagous arthropods have also adapted physiologically to ingest a food source that is relatively poor in vitamins and spiked with a cocktail of immunity factors. This cocktail also contains factors involved in the complement cascade, which is activated and mediated by a series of serine proteases . Activated by either the classical, alternative or lectin pathways, the cascade leads to the formation of pores across the plasma membrane of targeted cells. These pores ultimately cause the disruption of cellular compartmentalisation and lead to cell lysis.
Blood-borne pathogens typically evolve an intimate life-cycle with haematophagous arthropods that inadvertently become their vectors for transmission. As such, pathogens can often develop extensive interactions with their arthropod vectors where they modify their feeding behaviour or exploit pre-existing biological secretions from the vector to improve their chances of survival and transmission , , , . Here we described how PF trypanosomes benefit from the activity of tsetse serpin, GmmSRPN10, to avoid lysis by bloodmeal complement when in the fly’s midgut.