ArticleNature2013
Mechanism of Trypanosoma brucei gambiense resistance to human serum.
Article in Nature, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
79 citing papers in PubMed, 156 citations in OpenAlex.
- Apolipoproteins L involvement in immunity.Journal of human immunity · 2026Review
- Germline-targeted baboon apolipoprotein L-1 protects mice against African trypanosomes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Wildlife surveys detectCurrent research in parasitology & vector-borne diseases · 2026Article
- APOL1-mediated kidney disease: a narrative review of the lessons learnt from the past 15 years.BMC nephrology · 2025Review
- A novelRenal failure · 2025Article
- De novo rates of aProceedings of the National Academy of Sciences of the United States of America · 2025Article
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- Transforming the chemotherapy of human African trypanosomiasis.Clinical microbiology reviews · 2025Review
- Review
- Q586B2 is a crucial virulence factor during the early stages of Trypanosoma brucei infection that is conserved amongst trypanosomatids.Nature communications · 2024Article
- Advances in the Immunology of the Host-Parasite Interactions in African Trypanosomosis, including Single-Cell Transcriptomics.Pathogens (Basel, Switzerland) · 2024Review
- Pathogenicity and virulence of African trypanosomes: From laboratory models to clinically relevant hosts.Virulence · 2023Review
- Cryo-EM structures of Trypanosoma brucei gambiense ISG65 with human complement C3 and C3b and their roles in alternative pathway restriction.Nature communications · 2023Article
- Is there still evolution in the human population?Biologia futura · 2022Review
- Heme-deficient metabolism and impaired cellular differentiation as an evolutionary trade-off for human infectivity in Trypanosoma brucei gambiense.Nature communications · 2022Article
- ADAR regulates APOL1 via A-to-I RNA editing by inhibition of MDA5 activation in a paradoxical biological circuit.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- LncRNAs Are Differentially Expressed between Wildtype and Cell Line Strains of African Trypanosomes.Non-coding RNA · 2022Article
- An Update on African Trypanocide Pharmaceutics and Resistance.Frontiers in veterinary science · 2022Review
- Genetic and immunological basis of human African trypanosomiasis.Current opinion in immunology · 2021Review
- Salivarian Trypanosomes Have Adopted Intricate Host-Pathogen Interaction Mechanisms That Ensure Survival in Plain Sight of the Adaptive Immune System.Pathogens (Basel, Switzerland) · 2021Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 6 institutions in 5 countries.
Funding
Abstract
The African parasite Trypanosoma brucei gambiense accounts for 97% of human sleeping sickness cases. T. b. gambiense resists the specific human innate immunity acting against several other tsetse-fly-transmitted trypanosome species such as T. b. brucei, the causative agent of nagana disease in cattle. Human immunity to some African trypanosomes is due to two serum complexes designated trypanolytic factors (TLF-1 and -2), which both contain haptoglobin-related protein (HPR) and apolipoprotein LI (APOL1). Whereas HPR association with haemoglobin (Hb) allows TLF-1 binding and uptake via the trypanosome receptor TbHpHbR (ref. 5), TLF-2 enters trypanosomes independently of TbHpHbR (refs 4, 5). APOL1 kills trypanosomes after insertion into endosomal/lysosomal membranes. Here we report that T. b. gambiense resists TLFs via a hydrophobic β-sheet of the T. b. gambiense-specific glycoprotein (TgsGP), which prevents APOL1 toxicity and induces stiffening of membranes upon interaction with lipids. Two additional features contribute to resistance to TLFs: reduction of sensitivity to APOL1 requiring cysteine protease activity, and TbHpHbR inactivation due to a L210S substitution. According to such a multifactorial defence mechanism, transgenic expression of T. b. brucei TbHpHbR in T. b. gambiense did not cause parasite lysis in normal human serum. However, these transgenic parasites were killed in hypohaptoglobinaemic serum, after high TLF-1 uptake in the absence of haptoglobin (Hp) that competes for Hb and receptor binding. TbHpHbR inactivation preventing high APOL1 loading in hypohaptoglobinaemic serum may have evolved because of the overlapping endemic area of T. b. gambiense infection and malaria, the main cause of haemolysis-induced hypohaptoglobinaemia in western and central Africa.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.