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...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-09-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1005852&type=printable |
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| author | Mary-Anne Hartley Eliane Bourreau Matteo Rossi Patrik Castiglioni Remzi Onur Eren Florence Prevel Pierre Couppié Suzanne M Hickerson Pascal Launois Stephen M Beverley Catherine Ronet Nicolas Fasel |
| author_facet | Mary-Anne Hartley Eliane Bourreau Matteo Rossi Patrik Castiglioni Remzi Onur Eren Florence Prevel Pierre Couppié Suzanne M Hickerson Pascal Launois Stephen M Beverley Catherine Ronet Nicolas Fasel |
| author_sort | Mary-Anne Hartley |
| collection | DOAJ |
| 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 | Article |
| id | doaj-art-0a44ffda5fb54cbb8624a4f7be6a9e16 |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2016-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-0a44ffda5fb54cbb8624a4f7be6a9e162025-08-20T02:31:59ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742016-09-01129e100585210.1371/journal.ppat.1005852Leishmaniavirus-Dependent Metastatic Leishmaniasis Is Prevented by Blocking IL-17A.Mary-Anne HartleyEliane BourreauMatteo RossiPatrik CastiglioniRemzi Onur ErenFlorence PrevelPierre CouppiéSuzanne M HickersonPascal LaunoisStephen M BeverleyCatherine RonetNicolas FaselCutaneous 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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1005852&type=printable |
| spellingShingle | Mary-Anne Hartley Eliane Bourreau Matteo Rossi Patrik Castiglioni Remzi Onur Eren Florence Prevel Pierre Couppié Suzanne M Hickerson Pascal Launois Stephen M Beverley Catherine Ronet Nicolas Fasel Leishmaniavirus-Dependent Metastatic Leishmaniasis Is Prevented by Blocking IL-17A. PLoS Pathogens |
| 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 |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1005852&type=printable |
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