ArticleProceedings of the National Academy of Sciences of the United States of America2010
Mechanism of Trypanosoma brucei gambiense (group 1) resistance to human trypanosome lytic factor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed.
- Sleep-Wake Dysregulation in Human African Trypanosomiasis: From Neuroinvasion to Neuronal Dysfunction.Clocks & sleep · 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
- Transforming the chemotherapy of human African trypanosomiasis.Clinical microbiology reviews · 2025Review
- Mono-allelic epigenetic regulation of polycistronic transcription initiation by RNA polymerase II inmBio · 2025Article
- Heme-deficient metabolism and impaired cellular differentiation as an evolutionary trade-off for human infectivity in Trypanosoma brucei gambiense.Nature communications · 2022Article
- LncRNAs Are Differentially Expressed between Wildtype and Cell Line Strains of African Trypanosomes.Non-coding RNA · 2022Article
- Salivarian Trypanosomes Have Adopted Intricate Host-Pathogen Interaction Mechanisms That Ensure Survival in Plain Sight of the Adaptive Immune System.Pathogens (Basel, Switzerland) · 2021Review
- A single dose of antibody-drug conjugate cures a stage 1 model of African trypanosomiasis.PLoS neglected tropical diseases · 2019Article
- Decoding the network of Trypanosoma brucei proteins that determines sensitivity to apolipoprotein-L1.PLoS pathogens · 2018Article
- The Diversity of Mammalian Hemoproteins and Microbial Heme Scavengers Is Shaped by an Arms Race for Iron Piracy.Frontiers in immunology · 2018Article
- African Trypanosomiasis-Associated Anemia: The Contribution of the Interplay between Parasites and the Mononuclear Phagocyte System.Frontiers in immunology · 2018Review
- Salivarian Trypanosomosis: A Review of Parasites Involved, Their Global Distribution and Their Interaction With the Innate and Adaptive Mammalian Host Immune System.Frontiers in immunology · 2018Review
- Pathways to zoonotic spillover.Nature reviews. Microbiology · 2017Review
- Candidate gene polymorphisms study between human African trypanosomiasis clinical phenotypes in Guinea.PLoS neglected tropical diseases · 2017Article
- Article
- A Receptor's Tale: An Eon in the Life of a Trypanosome Receptor.PLoS pathogens · 2017Review
- A Primate APOL1 Variant That Kills Trypanosoma brucei gambiense.PLoS neglected tropical diseases · 2016Article
- An Overview ofFrontiers in microbiology · 2016Review
- Immune Evasion Strategies of Trypanosoma brucei within the Mammalian Host: Progression to Pathogenicity.Frontiers in immunology · 2016Review
- Role of cytokines in Trypanosoma brucei-induced anaemia: A review of the literature.Malawi medical journal : the journal of Medical Association of Malawi · 2015Review
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Authors and funding
6 authors.
Funding
Abstract
Human innate immunity against most African trypanosomes, including Trypanosoma brucei brucei, is mediated by a minor subclass of toxic serum HDL, called trypanosome lytic factor-1 (TLF-1). This HDL contains two primate specific proteins, apolipoprotein L-1 and haptoglobin (Hp)-related protein, as well as apolipoprotein A-1. These assembled proteins provide a powerful defense against trypanosome infection. Trypanosoma brucei rhodesiense causes human African sleeping sickness because it has evolved an inhibitor of TLF-1, serum resistance-associated (SRA) protein. Trypanosoma brucei gambiense lacks the SRA gene, yet it infects humans. As transfection of T. b. gambiense (group 1) is not possible, we initially used in vitro-selected TLF-1-resistant T. b. brucei to examine SRA-independent mechanisms of TLF-1 resistance. Here we show that TLF-1 resistance in T. b. brucei is caused by reduced expression of the Hp/Hb receptor gene (TbbHpHbR). Importantly, T. b. gambiense (group 1) also showed a marked reduction in uptake of TLF-1 and a corresponding decrease in expression of T. b. gambiense Hp/Hb receptor (TbgHpHbR). Ectopic expression of TbbHpHbR in TLF-1-resistant T. b. brucei rescued TLF-1 uptake, demonstrating that decreased TbbHpHbR expression conferred TLF-1 resistance. Ectopic expression of TbgHpHbR in TLF-1-resistant T. b. brucei failed to rescue TLF-1 killing, suggesting that coding sequence changes altered Hp/Hb receptor binding affinity for TLF-1. We propose that the combination of coding sequence mutations and decreased expression of TbgHpHbR directly contribute to parasite evasion of human innate immunity and infectivity of group 1 T. b. gambiense.
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