The Eukaryotic Elongation Factor 1 Alpha (eEF1α) from the Parasite Leishmania infantum Is Modified with the Immunomodulatory Substituent Phosphorylcholine (PC)

Proteins and glycolipids have been found to be decorated with phosphorylcholine (PC) both in protozoa and nematodes that parasitize humans and animals. PC epitopes can provoke various effects on immune cells leading to an immunomodulation of the host’s immune system that allows long-term persistence...

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Main Authors: Thomas Timm, Giada Annoscia, Jochen Klein, Günter Lochnit
Format: Article
Language:English
Published: MDPI AG 2017-11-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/22/12/2094
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author Thomas Timm
Giada Annoscia
Jochen Klein
Günter Lochnit
author_facet Thomas Timm
Giada Annoscia
Jochen Klein
Günter Lochnit
author_sort Thomas Timm
collection DOAJ
description Proteins and glycolipids have been found to be decorated with phosphorylcholine (PC) both in protozoa and nematodes that parasitize humans and animals. PC epitopes can provoke various effects on immune cells leading to an immunomodulation of the host’s immune system that allows long-term persistence of the parasites. So far, only a limited number of PC-modified proteins, mainly from nematodes, have been identified. Infections caused by Leishmania spp. (e.g., L. infantum in southern Europe) affect about 12 million people worldwide and are characterized by a wide spectrum of clinical forms in humans, ranging from cutaneous to fatal visceral leishmaniasis. To establish and maintain the infection, these protozoa are dependent on the secretion of effector molecules into the host for modulating their immune system. In this project, we analyzed the PC modification of L. infantum promastigotes by 2D-gel based proteomics. Western blot analysis with the PC-specific antibody TEPC-15 revealed one PC-substituted protein in this organism, identified as eEF1α. We could demonstrate that the binding of eEF1α to one of its downstream effectors is dependent on its PC-modification. In this study we provide evidence that in this parasite the modification of eEF1α with PC may be essential for its function as an important virulence factor.
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spelling doaj.art-a3775e6f8c8f4cbf8614ad411b824cc72022-12-22T03:37:08ZengMDPI AGMolecules1420-30492017-11-012212209410.3390/molecules22122094molecules22122094The Eukaryotic Elongation Factor 1 Alpha (eEF1α) from the Parasite Leishmania infantum Is Modified with the Immunomodulatory Substituent Phosphorylcholine (PC)Thomas Timm0Giada Annoscia1Jochen Klein2Günter Lochnit3Protein Analytics, Institute of Biochemistry, Faculty of Medicine, Justus-Liebig-University Giessen, Friedrichstrasse 24, 35392 Giessen, GermanyDepartment of Veterinary Medicine, University of Bari, Str. prov. per Casamassima km 3, Valenzano, 70010 Bari, ItalyDepartment of Pharmacology, Goethe University College of Pharmacy, 60438 Frankfurt, GermanyProtein Analytics, Institute of Biochemistry, Faculty of Medicine, Justus-Liebig-University Giessen, Friedrichstrasse 24, 35392 Giessen, GermanyProteins and glycolipids have been found to be decorated with phosphorylcholine (PC) both in protozoa and nematodes that parasitize humans and animals. PC epitopes can provoke various effects on immune cells leading to an immunomodulation of the host’s immune system that allows long-term persistence of the parasites. So far, only a limited number of PC-modified proteins, mainly from nematodes, have been identified. Infections caused by Leishmania spp. (e.g., L. infantum in southern Europe) affect about 12 million people worldwide and are characterized by a wide spectrum of clinical forms in humans, ranging from cutaneous to fatal visceral leishmaniasis. To establish and maintain the infection, these protozoa are dependent on the secretion of effector molecules into the host for modulating their immune system. In this project, we analyzed the PC modification of L. infantum promastigotes by 2D-gel based proteomics. Western blot analysis with the PC-specific antibody TEPC-15 revealed one PC-substituted protein in this organism, identified as eEF1α. We could demonstrate that the binding of eEF1α to one of its downstream effectors is dependent on its PC-modification. In this study we provide evidence that in this parasite the modification of eEF1α with PC may be essential for its function as an important virulence factor.https://www.mdpi.com/1420-3049/22/12/2094Leishmania infantumpromastigoteproteomicsphosphorylcholineimmunomodulationimmunofluorescence
spellingShingle Thomas Timm
Giada Annoscia
Jochen Klein
Günter Lochnit
The Eukaryotic Elongation Factor 1 Alpha (eEF1α) from the Parasite Leishmania infantum Is Modified with the Immunomodulatory Substituent Phosphorylcholine (PC)
Molecules
Leishmania infantum
promastigote
proteomics
phosphorylcholine
immunomodulation
immunofluorescence
title The Eukaryotic Elongation Factor 1 Alpha (eEF1α) from the Parasite Leishmania infantum Is Modified with the Immunomodulatory Substituent Phosphorylcholine (PC)
title_full The Eukaryotic Elongation Factor 1 Alpha (eEF1α) from the Parasite Leishmania infantum Is Modified with the Immunomodulatory Substituent Phosphorylcholine (PC)
title_fullStr The Eukaryotic Elongation Factor 1 Alpha (eEF1α) from the Parasite Leishmania infantum Is Modified with the Immunomodulatory Substituent Phosphorylcholine (PC)
title_full_unstemmed The Eukaryotic Elongation Factor 1 Alpha (eEF1α) from the Parasite Leishmania infantum Is Modified with the Immunomodulatory Substituent Phosphorylcholine (PC)
title_short The Eukaryotic Elongation Factor 1 Alpha (eEF1α) from the Parasite Leishmania infantum Is Modified with the Immunomodulatory Substituent Phosphorylcholine (PC)
title_sort eukaryotic elongation factor 1 alpha eef1α from the parasite leishmania infantum is modified with the immunomodulatory substituent phosphorylcholine pc
topic Leishmania infantum
promastigote
proteomics
phosphorylcholine
immunomodulation
immunofluorescence
url https://www.mdpi.com/1420-3049/22/12/2094
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