ArticlePLoS pathogens2009
Trypanosome lytic factor, an antimicrobial high-density lipoprotein, ameliorates Leishmania infection.
Article in PLoS pathogens, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- APOL1 variant alleles associate with reduced risk for opportunistic infections in HIV infection.Communications biology · 2021Pooled it
- Partially Replacing Dietary Carbohydrate With Unsaturated Fat or Protein Shifts Protein-Based HDL Subspecies Toward Lower Coronary Heart Disease Risk.Arteriosclerosis, thrombosis, and vascular biology · 2026Trial
- 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
- Lipidome and proteome of astrocyte and microglia ApoE lipoprotein reveal differences based on cell type and ApoE isoform.Journal of lipid research · 2026Article
- Design of a novel multi epitope antigen for diagnosis of visceral leishmaniasis using an immunoinformatics approach.Scientific reports · 2025Article
- Reduced Cholesterol Levels during Acute Human Babesiosis.Pathogens (Basel, Switzerland) · 2023Article
- High Density Lipoproteins: Is There a Comeback as a Therapeutic Target?Handbook of experimental pharmacology · 2022Article
- Evolutionary genetics and acclimatization in nephrology.Nature reviews. Nephrology · 2021Review
- Interplay of Trypanosome Lytic Factor and innate immune cells in the resolution of cutaneous Leishmania infection.PLoS pathogens · 2021Article
- The Role of High-Density Lipoprotein in COVID-19.Frontiers in pharmacology · 2021Review
- Cation channel conductance and pH gating of the innate immunity factor APOL1 are governed by pore-lining residues within the C-terminal domain.The Journal of biological chemistry · 2020Article
- Domain-Specific Antibodies Reveal Differences in the Membrane Topologies of Apolipoprotein L1 in Serum and Podocytes.Journal of the American Society of Nephrology : JASN · 2020Article
- Apolipoprotein L-1 renal risk variants form active channels at the plasma membrane driving cytotoxicity.eLife · 2020Article
- High-Density Lipoproteins Are Bug Scavengers.Biomolecules · 2020Review
- G1 is the majorClinical kidney journal · 2019Article
- APOL1 polymorphisms and kidney disease: loss-of-function or gain-of-function?American journal of physiology. Renal physiology · 2019Review
- APOL1-Associated Nephropathy: A Key Contributor to Racial Disparities in CKD.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2018Review
- ApoL1 renal risk variants induce aberrant THP-1 monocyte differentiation and increase eicosanoid production via enhanced expression of cyclooxygenase-2.American journal of physiology. Renal physiology · 2018Article
- Shape, form, function andOpen biology · 2017Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Innate immunity is the first line of defense against invading microorganisms. Trypanosome Lytic Factor (TLF) is a minor sub-fraction of human high-density lipoprotein that provides innate immunity by completely protecting humans from infection by most species of African trypanosomes, which belong to the Kinetoplastida order. Herein, we demonstrate the broader protective effects of human TLF, which inhibits intracellular infection by Leishmania, a kinetoplastid that replicates in phagolysosomes of macrophages. We show that TLF accumulates within the parasitophorous vacuole of macrophages in vitro and reduces the number of Leishmania metacyclic promastigotes, but not amastigotes. We do not detect any activation of the macrophages by TLF in the presence or absence of Leishmania, and therefore propose that TLF directly damages the parasite in the acidic parasitophorous vacuole. To investigate the physiological relevance of this observation, we have reconstituted lytic activity in vivo by generating mice that express the two main protein components of TLFs: human apolipoprotein L-I and haptoglobin-related protein. Both proteins are expressed in mice at levels equivalent to those found in humans and circulate within high-density lipoproteins. We find that TLF mice can ameliorate an infection with Leishmania by significantly reducing the pathogen burden. In contrast, TLF mice were not protected against infection by the kinetoplastid Trypanosoma cruzi, which infects many cell types and transiently passes through a phagolysosome. We conclude that TLF not only determines species specificity for African trypanosomes, but can also ameliorate an infection with Leishmania, while having no effect on T. cruzi. We propose that TLFs are a component of the innate immune system that can limit infections by their ability to selectively damage pathogens in phagolysosomes within the reticuloendothelial system.
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Registered trials
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