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dc.contributor.authorSamanovic, Marie
dc.contributor.authorMolina-Portela, Maria Pilar
dc.contributor.authorChessler, Anne-Danielle C.
dc.contributor.authorBurleigh, Barbara
dc.contributor.authorRaper, Jayne
dc.date.accessioned2010-11-18T19:07:44Z
dc.date.issued2009
dc.identifier.citationSamanovic, Marie, Maria Pilar Molina-Portela, Anne-Danielle C. Chessler, Barbara A. Burleigh, and Jayne Raper. 2009. Trypanosome lytic factor, an antimicrobial high-density lipoprotein, ameliorates Leishmania infection. PLoS Pathogens 5(1): e1000276.en_US
dc.identifier.issn1553-7366en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4582588
dc.description.abstractInnate 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.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.ppat.1000276en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2622765/pdf/en_US
dash.licenseLAA
dc.subjectbiochemistryen_US
dc.subjectbiomacromolecule-ligand interactionsen_US
dc.subjectcell biologyen_US
dc.subjectmicrobial growth and developmenten_US
dc.subjectimmunologyen_US
dc.subjectimmunity to infectionsen_US
dc.subjectinnate immunityen_US
dc.subjectinfectious diseasesen_US
dc.subjectneglected tropical diseasesen_US
dc.subjectprotozoal infectionsen_US
dc.subjectmicrobiologyen_US
dc.subjectparasitologyen_US
dc.titleTrypanosome Lytic Factor, an Antimicrobial High-Density Lipoprotein, Ameliorates Leishmania Infectionen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Pathogensen_US
dash.depositing.authorBurleigh, Barbara
dc.date.available2010-11-18T19:07:44Z
dash.affiliation.otherSPH^Malaria/Wirthen_US
dc.identifier.doi10.1371/journal.ppat.1000276*
dash.contributor.affiliatedBurleigh, Barbara


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