Abstract
Trypanosoma brucei rhodesiense (Tbr) and T. b. gambiense (Tbg), causative agents of Human African Trypanosomiasis (sleeping sickness) in Africa, have evolved alternative mechanisms of resisting the activity of trypanosome lytic factors (TLFs), components of innate immunity in human serum that protect against infection by other African trypanosomes. In Tbr, lytic activity is suppressed by the Tbr-specific serum-resistance associated (SRA) protein. The mechanism in Tbg is less well understood but has been hypothesized to involve altered activity and expression of haptoglobin haemoglobin receptor (HpHbR). HpHbR has been shown to facilitate internalization of TLF-1 in T.b. brucei (Tbb), a member of the T. brucei species complex that is susceptible to human serum. By evaluating the genetic variability of HpHbR in a comprehensive geographical and taxonomic context, we show that a single substitution that replaces leucine with serine at position 210 is conserved in the most widespread form of Tbg (Tbg group 1) and not found in related taxa, which are either human serum susceptible (Tbb) or known to resist lysis via an alternative mechanism (Tbr and Tbg group 2). We hypothesize that this single substitution contributes to reduced uptake of TLF and thus may play a key role in conferring serum resistance to Tbg group 1. In contrast, similarity in HpHbR sequence among isolates of Tbg group 2 and Tbb/Tbr provides further evidence that human serum resistance in Tbg group 2 is likely independent of HpHbR function.
Highlights
Trypanosomiasis, a deadly disease of humans and livestock in sub-Saharan Africa, is caused by protozoan parasites of the genus Trypanosoma, which are transmitted between mammalian hosts by insect vectors of the genus Glossina
In T. b. gambiense (Tbg) group 1, which causes the vast majority of disease cases, the mechanism is thought to involve the reduced activity of a receptor involved in binding and internalizing trypanosome lytic factors (TLFs)
We investigate genetic variation in this receptor across a broad geographic sample of Tbg and closely related trypanosomes to test whether unique polymorphisms in the receptor from Tbg may explain its altered function
Summary
Trypanosomiasis, a deadly disease of humans and livestock in sub-Saharan Africa, is caused by protozoan parasites of the genus Trypanosoma, which are transmitted between mammalian hosts by insect vectors of the genus Glossina (tsetse). Human-infective members of the Trypanosoma brucei complex cause the human form of the disease, Human African Trypanosomiasis (HAT), or sleeping sickness. Gambiense group 2 (Tbg2), a rare form described from West Africa in the 1970s and 1980s, causes human disease but the trait of human-infectivity is not stable [1,2,3]. Brucei (Tbb), is not infective to humans, but, together with other animal trypanosome species, causes the livestock wasting disease, Nagana, across a range that overlaps with that of the humaninfective parasites. While Tbb is susceptible to lysis by human TLF-1, Tbr, Tbg and Tbg are resistant. In Tbr, the serum-resistance associated (SRA) protein confers resistance to TLF-1 [8] by binding directly to apoL-I after it has been internalized into the cell, inhibiting its lysosome-lytic capacity [9]. Tbg and Tbg, on the other hand, lack the gene encoding SRA and are thought to have evolved an independent mechanism to prevent lysis by TLF
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
