ArticlePLoS pathogens2013
A single amino acid substitution in the group 1 Trypanosoma brucei gambiense haptoglobin-hemoglobin receptor abolishes TLF-1 binding.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 54 citations in OpenAlex.
- Mono-allelic epigenetic regulation of polycistronic transcription initiation by RNA polymerase II inmBio · 2025Article
- Advances in the Immunology of the Host-Parasite Interactions in African Trypanosomosis, including Single-Cell Transcriptomics.Pathogens (Basel, Switzerland) · 2024Review
- 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
- 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
- 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
- The Diversity of Mammalian Hemoproteins and Microbial Heme Scavengers Is Shaped by an Arms Race for Iron Piracy.Frontiers in immunology · 2018Article
- A polymorphism in the haptoglobin, haptoglobin related protein locus is associated with risk of human sleeping sickness within Cameroonian populations.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
- Characterization of an epimastigote-stage-specific hemoglobin receptor of Trypanosoma congolense.Parasites & vectors · 2016Article
- Article
- Trypanosome Lytic Factor-1 Initiates Oxidation-stimulated Osmotic Lysis of Trypanosoma brucei brucei.The Journal of biological chemistry · 2016Article
- Immune Evasion Strategies of Trypanosoma brucei within the Mammalian Host: Progression to Pathogenicity.Frontiers in immunology · 2016Review
- A co-evolutionary arms race: trypanosomes shaping the human genome, humans shaping the trypanosome genome.Parasitology · 2015Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Critical to human innate immunity against African trypanosomes is a minor subclass of human high-density lipoproteins, termed Trypanosome Lytic Factor-1 (TLF-1). This primate-specific molecule binds to a haptoglobin-hemoglobin receptor (HpHbR) on the surface of susceptible trypanosomes, initiating a lytic pathway. Group 1 Trypanosoma brucei gambiense causes human African Trypanosomiasis (HAT), escaping TLF-1 killing due to reduced uptake. Previously, we found that group 1 T. b. gambiense HpHbR (TbgHpHbR) mRNA levels were greatly reduced and the gene contained substitutions within the open reading frame. Here we show that a single, highly conserved amino acid in the TbgHpHbR ablates high affinity TLF-1 binding and subsequent endocytosis, thus evading TLF-1 killing. In addition, we show that over-expression of TbgHpHbR failed to rescue TLF-1 susceptibility. These findings suggest that the single substitution present in the TbgHpHbR directly contributes to the reduced uptake and resistance to TLF-1 seen in these important human pathogens.
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Registered trials
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.