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Leishmaniavirus-Dependent Metastatic Leishmaniasis Is Prevented by Blocking IL-17A
Cutaneous leishmaniasis has various outcomes, ranging from self-healing reddened papules to extensive open ulcerations that metastasise to secondary sites and are often resistant to standard therapies. In the case of L. guyanensis (L.g), about 5–10% of all infections result in metastatic complicatio...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033371/ https://www.ncbi.nlm.nih.gov/pubmed/27658195 http://dx.doi.org/10.1371/journal.ppat.1005852 |
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author | Hartley, Mary-Anne Bourreau, Eliane Rossi, Matteo Castiglioni, Patrik Eren, Remzi Onur Prevel, Florence Couppié, Pierre Hickerson, Suzanne M. Launois, Pascal Beverley, Stephen M. Ronet, Catherine Fasel, Nicolas |
author_facet | Hartley, Mary-Anne Bourreau, Eliane Rossi, Matteo Castiglioni, Patrik Eren, Remzi Onur Prevel, Florence Couppié, Pierre Hickerson, Suzanne M. Launois, Pascal Beverley, Stephen M. Ronet, Catherine Fasel, Nicolas |
author_sort | Hartley, Mary-Anne |
collection | PubMed |
description | Cutaneous leishmaniasis has various outcomes, ranging from self-healing reddened papules to extensive open ulcerations that metastasise to secondary sites and are often resistant to standard therapies. In the case of L. guyanensis (L.g), about 5–10% of all infections result in metastatic complications. We recently showed that a cytoplasmic virus within L.g parasites (LRV1) is able to act as a potent innate immunogen, worsening disease outcome in a murine model. In this study, we investigated the immunophenotype of human patients infected by L.g and found a significant association between the inflammatory cytokine IL-17A, the presence of LRV1 and disease chronicity. Further, IL-17A was inversely correlated to the protective cytokine IFN-γ. These findings were experimentally corroborated in our murine model, where IL-17A produced in LRV1+ L.g infection contributed to parasite virulence and dissemination in the absence of IFN-γ. Additionally, IL-17A inhibition in mice using digoxin or SR1001, showed therapeutic promise in limiting parasite virulence. Thus, this murine model of LRV1-dependent infectious metastasis validated markers of disease chronicity in humans and elucidated the immunologic mechanism for the dissemination of Leishmania parasites to secondary sites. Moreover, it confirms the prognostic value of LRV1 and IL-17A detection to prevent metastatic leishmaniasis in human patients. |
format | Online Article Text |
id | pubmed-5033371 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-50333712016-10-10 Leishmaniavirus-Dependent Metastatic Leishmaniasis Is Prevented by Blocking IL-17A Hartley, Mary-Anne Bourreau, Eliane Rossi, Matteo Castiglioni, Patrik Eren, Remzi Onur Prevel, Florence Couppié, Pierre Hickerson, Suzanne M. Launois, Pascal Beverley, Stephen M. Ronet, Catherine Fasel, Nicolas PLoS Pathog Research Article Cutaneous leishmaniasis has various outcomes, ranging from self-healing reddened papules to extensive open ulcerations that metastasise to secondary sites and are often resistant to standard therapies. In the case of L. guyanensis (L.g), about 5–10% of all infections result in metastatic complications. We recently showed that a cytoplasmic virus within L.g parasites (LRV1) is able to act as a potent innate immunogen, worsening disease outcome in a murine model. In this study, we investigated the immunophenotype of human patients infected by L.g and found a significant association between the inflammatory cytokine IL-17A, the presence of LRV1 and disease chronicity. Further, IL-17A was inversely correlated to the protective cytokine IFN-γ. These findings were experimentally corroborated in our murine model, where IL-17A produced in LRV1+ L.g infection contributed to parasite virulence and dissemination in the absence of IFN-γ. Additionally, IL-17A inhibition in mice using digoxin or SR1001, showed therapeutic promise in limiting parasite virulence. Thus, this murine model of LRV1-dependent infectious metastasis validated markers of disease chronicity in humans and elucidated the immunologic mechanism for the dissemination of Leishmania parasites to secondary sites. Moreover, it confirms the prognostic value of LRV1 and IL-17A detection to prevent metastatic leishmaniasis in human patients. Public Library of Science 2016-09-22 /pmc/articles/PMC5033371/ /pubmed/27658195 http://dx.doi.org/10.1371/journal.ppat.1005852 Text en © 2016 Hartley et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Hartley, Mary-Anne Bourreau, Eliane Rossi, Matteo Castiglioni, Patrik Eren, Remzi Onur Prevel, Florence Couppié, Pierre Hickerson, Suzanne M. Launois, Pascal Beverley, Stephen M. Ronet, Catherine Fasel, Nicolas Leishmaniavirus-Dependent Metastatic Leishmaniasis Is Prevented by Blocking IL-17A |
title |
Leishmaniavirus-Dependent Metastatic Leishmaniasis Is Prevented by Blocking IL-17A |
title_full |
Leishmaniavirus-Dependent Metastatic Leishmaniasis Is Prevented by Blocking IL-17A |
title_fullStr |
Leishmaniavirus-Dependent Metastatic Leishmaniasis Is Prevented by Blocking IL-17A |
title_full_unstemmed |
Leishmaniavirus-Dependent Metastatic Leishmaniasis Is Prevented by Blocking IL-17A |
title_short |
Leishmaniavirus-Dependent Metastatic Leishmaniasis Is Prevented by Blocking IL-17A |
title_sort | leishmaniavirus-dependent metastatic leishmaniasis is prevented by blocking il-17a |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033371/ https://www.ncbi.nlm.nih.gov/pubmed/27658195 http://dx.doi.org/10.1371/journal.ppat.1005852 |
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