Trypanosomatid Infections: How Do Parasites and Their Excreted–Secreted Factors Modulate the Inducible Metabolism of l-Arginine in Macrophages?
Mononuclear phagocytes (monocytes, dendritic cells, and macrophages) are among the first host cells to face intra- and extracellular protozoan parasites such as trypanosomatids, and significant expansion of macrophages has been observed in infected hosts. They play essential roles in the outcome of...
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Frontiers Media S.A.
2018-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00778/full |
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| author | Philippe Holzmuller Philippe Holzmuller Anne Geiger Romaric Nzoumbou-Boko Romaric Nzoumbou-Boko Romaric Nzoumbou-Boko Joana Pissarra Sarra Hamrouni Valérie Rodrigues Valérie Rodrigues Frédéric-Antoine Dauchy Frédéric-Antoine Dauchy Frédéric-Antoine Dauchy Jean-Loup Lemesre Philippe Vincendeau Philippe Vincendeau Philippe Vincendeau Rachel Bras-Gonçalves |
| author_facet | Philippe Holzmuller Philippe Holzmuller Anne Geiger Romaric Nzoumbou-Boko Romaric Nzoumbou-Boko Romaric Nzoumbou-Boko Joana Pissarra Sarra Hamrouni Valérie Rodrigues Valérie Rodrigues Frédéric-Antoine Dauchy Frédéric-Antoine Dauchy Frédéric-Antoine Dauchy Jean-Loup Lemesre Philippe Vincendeau Philippe Vincendeau Philippe Vincendeau Rachel Bras-Gonçalves |
| author_sort | Philippe Holzmuller |
| collection | DOAJ |
| description | Mononuclear phagocytes (monocytes, dendritic cells, and macrophages) are among the first host cells to face intra- and extracellular protozoan parasites such as trypanosomatids, and significant expansion of macrophages has been observed in infected hosts. They play essential roles in the outcome of infections caused by trypanosomatids, as they can not only exert a powerful antimicrobial activity but also promote parasite proliferation. These varied functions, linked to their phenotypic and metabolic plasticity, are exerted via distinct activation states, in which l-arginine metabolism plays a pivotal role. Depending on the environmental factors and immune response elements, l-arginine metabolites contribute to parasite elimination, mainly through nitric oxide (NO) synthesis, or to parasite proliferation, through l-ornithine and polyamine production. To survive and adapt to their hosts, parasites such as trypanosomatids developed mechanisms of interaction to modulate macrophage activation in their favor, by manipulating several cellular metabolic pathways. Recent reports emphasize that some excreted–secreted (ES) molecules from parasites and sugar-binding host receptors play a major role in this dialog, particularly in the modulation of the macrophage’s inducible l-arginine metabolism. Preventing l-arginine dysregulation by drugs or by immunization against trypanosomatid ES molecules or by blocking partner host molecules may control early infection and is a promising way to tackle neglected diseases including Chagas disease, leishmaniases, and African trypanosomiases. The present review summarizes recent knowledge on trypanosomatids and their ES factors with regard to their influence on macrophage activation pathways, mainly the NO synthase/arginase balance. The review ends with prospects for the use of biological knowledge to develop new strategies of interference in the infectious processes used by trypanosomatids, in particular for the development of vaccines or immunotherapeutic approaches. |
| first_indexed | 2024-12-21T04:19:40Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-21T04:19:40Z |
| publishDate | 2018-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-2e953df2a2e748c7bae80f6bec7d98782022-12-21T19:16:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-04-01910.3389/fimmu.2018.00778328253Trypanosomatid Infections: How Do Parasites and Their Excreted–Secreted Factors Modulate the Inducible Metabolism of l-Arginine in Macrophages?Philippe Holzmuller0Philippe Holzmuller1Anne Geiger2Romaric Nzoumbou-Boko3Romaric Nzoumbou-Boko4Romaric Nzoumbou-Boko5Joana Pissarra6Sarra Hamrouni7Valérie Rodrigues8Valérie Rodrigues9Frédéric-Antoine Dauchy10Frédéric-Antoine Dauchy11Frédéric-Antoine Dauchy12Jean-Loup Lemesre13Philippe Vincendeau14Philippe Vincendeau15Philippe Vincendeau16Rachel Bras-Gonçalves17CIRAD, Montpellier, FranceUMR 117 ASTRE “Animal, Santé, Territoire, Risques et Ecosystèmes”, Univ. Montpellier (I-MUSE), CIRAD, INRA, Montpellier, FranceUMR 177 INTERTRYP “Interactions Hôte-Vecteur-Parasite-Environnement dans les maladies tropicales négligées dues aux Trypanosomatidae”, Univ. Montpellier (I-MUSE), CIRAD, IRD, Univ. Bordeaux 2, Univ. Lyon 1, Montpellier, FranceUMR 177 INTERTRYP “Interactions Hôte-Vecteur-Parasite-Environnement dans les maladies tropicales négligées dues aux Trypanosomatidae”, Univ. Montpellier (I-MUSE), CIRAD, IRD, Univ. Bordeaux 2, Univ. Lyon 1, Montpellier, FranceUniv. Bordeaux, UMR 177 INTERTRYP, Bordeaux, FranceCHU Bordeaux, Laboratoire de Parasitologie-Mycologie, Bordeaux, FranceUMR 177 INTERTRYP “Interactions Hôte-Vecteur-Parasite-Environnement dans les maladies tropicales négligées dues aux Trypanosomatidae”, Univ. Montpellier (I-MUSE), CIRAD, IRD, Univ. Bordeaux 2, Univ. Lyon 1, Montpellier, FranceUMR 177 INTERTRYP “Interactions Hôte-Vecteur-Parasite-Environnement dans les maladies tropicales négligées dues aux Trypanosomatidae”, Univ. Montpellier (I-MUSE), CIRAD, IRD, Univ. Bordeaux 2, Univ. Lyon 1, Montpellier, FranceCIRAD, Montpellier, FranceUMR 117 ASTRE “Animal, Santé, Territoire, Risques et Ecosystèmes”, Univ. Montpellier (I-MUSE), CIRAD, INRA, Montpellier, FranceUMR 177 INTERTRYP “Interactions Hôte-Vecteur-Parasite-Environnement dans les maladies tropicales négligées dues aux Trypanosomatidae”, Univ. Montpellier (I-MUSE), CIRAD, IRD, Univ. Bordeaux 2, Univ. Lyon 1, Montpellier, FranceUniv. Bordeaux, UMR 177 INTERTRYP, Bordeaux, FranceCHU Bordeaux, Département des Maladies Infectieuses et Tropicales, Bordeaux, FranceUMR 177 INTERTRYP “Interactions Hôte-Vecteur-Parasite-Environnement dans les maladies tropicales négligées dues aux Trypanosomatidae”, Univ. Montpellier (I-MUSE), CIRAD, IRD, Univ. Bordeaux 2, Univ. Lyon 1, Montpellier, FranceUMR 177 INTERTRYP “Interactions Hôte-Vecteur-Parasite-Environnement dans les maladies tropicales négligées dues aux Trypanosomatidae”, Univ. Montpellier (I-MUSE), CIRAD, IRD, Univ. Bordeaux 2, Univ. Lyon 1, Montpellier, FranceUniv. Bordeaux, UMR 177 INTERTRYP, Bordeaux, FranceCHU Bordeaux, Laboratoire de Parasitologie-Mycologie, Bordeaux, FranceUMR 177 INTERTRYP “Interactions Hôte-Vecteur-Parasite-Environnement dans les maladies tropicales négligées dues aux Trypanosomatidae”, Univ. Montpellier (I-MUSE), CIRAD, IRD, Univ. Bordeaux 2, Univ. Lyon 1, Montpellier, FranceMononuclear phagocytes (monocytes, dendritic cells, and macrophages) are among the first host cells to face intra- and extracellular protozoan parasites such as trypanosomatids, and significant expansion of macrophages has been observed in infected hosts. They play essential roles in the outcome of infections caused by trypanosomatids, as they can not only exert a powerful antimicrobial activity but also promote parasite proliferation. These varied functions, linked to their phenotypic and metabolic plasticity, are exerted via distinct activation states, in which l-arginine metabolism plays a pivotal role. Depending on the environmental factors and immune response elements, l-arginine metabolites contribute to parasite elimination, mainly through nitric oxide (NO) synthesis, or to parasite proliferation, through l-ornithine and polyamine production. To survive and adapt to their hosts, parasites such as trypanosomatids developed mechanisms of interaction to modulate macrophage activation in their favor, by manipulating several cellular metabolic pathways. Recent reports emphasize that some excreted–secreted (ES) molecules from parasites and sugar-binding host receptors play a major role in this dialog, particularly in the modulation of the macrophage’s inducible l-arginine metabolism. Preventing l-arginine dysregulation by drugs or by immunization against trypanosomatid ES molecules or by blocking partner host molecules may control early infection and is a promising way to tackle neglected diseases including Chagas disease, leishmaniases, and African trypanosomiases. The present review summarizes recent knowledge on trypanosomatids and their ES factors with regard to their influence on macrophage activation pathways, mainly the NO synthase/arginase balance. The review ends with prospects for the use of biological knowledge to develop new strategies of interference in the infectious processes used by trypanosomatids, in particular for the development of vaccines or immunotherapeutic approaches.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00778/fullmacrophage activationl-arginine metabolismarginasesecretometrypanosomatids |
| spellingShingle | Philippe Holzmuller Philippe Holzmuller Anne Geiger Romaric Nzoumbou-Boko Romaric Nzoumbou-Boko Romaric Nzoumbou-Boko Joana Pissarra Sarra Hamrouni Valérie Rodrigues Valérie Rodrigues Frédéric-Antoine Dauchy Frédéric-Antoine Dauchy Frédéric-Antoine Dauchy Jean-Loup Lemesre Philippe Vincendeau Philippe Vincendeau Philippe Vincendeau Rachel Bras-Gonçalves Trypanosomatid Infections: How Do Parasites and Their Excreted–Secreted Factors Modulate the Inducible Metabolism of l-Arginine in Macrophages? Frontiers in Immunology macrophage activation l-arginine metabolism arginase secretome trypanosomatids |
| title | Trypanosomatid Infections: How Do Parasites and Their Excreted–Secreted Factors Modulate the Inducible Metabolism of l-Arginine in Macrophages? |
| title_full | Trypanosomatid Infections: How Do Parasites and Their Excreted–Secreted Factors Modulate the Inducible Metabolism of l-Arginine in Macrophages? |
| title_fullStr | Trypanosomatid Infections: How Do Parasites and Their Excreted–Secreted Factors Modulate the Inducible Metabolism of l-Arginine in Macrophages? |
| title_full_unstemmed | Trypanosomatid Infections: How Do Parasites and Their Excreted–Secreted Factors Modulate the Inducible Metabolism of l-Arginine in Macrophages? |
| title_short | Trypanosomatid Infections: How Do Parasites and Their Excreted–Secreted Factors Modulate the Inducible Metabolism of l-Arginine in Macrophages? |
| title_sort | trypanosomatid infections how do parasites and their excreted secreted factors modulate the inducible metabolism of l arginine in macrophages |
| topic | macrophage activation l-arginine metabolism arginase secretome trypanosomatids |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00778/full |
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