Amazonian Phlebovirus (Bunyaviridae) potentiates the infection of Leishmania (Leishmania) amazonensis: Role of the PKR/IFN1/IL-10 axis.
Background Leishmania parasites are transmitted to vertebrate hosts by phlebotomine sandflies and, in humans, may cause tegumentary or visceral leishmaniasis. The role of PKR (dsRNA activated kinase) and Toll-like receptor 3 (TLR3) activation in the control of Leishmania infection highlights the imp...
Published in: | PLOS Neglected Tropical Diseases |
---|---|
Main Authors: | , , , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Public Library of Science (PLoS)
2019
|
Subjects: | |
Online Access: | https://doi.org/10.1371/journal.pntd.0007500 https://doaj.org/article/9bcc055464d548a2afe91ed032f6c070 |
id |
ftdoajarticles:oai:doaj.org/article:9bcc055464d548a2afe91ed032f6c070 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:9bcc055464d548a2afe91ed032f6c070 2023-05-15T15:13:13+02:00 Amazonian Phlebovirus (Bunyaviridae) potentiates the infection of Leishmania (Leishmania) amazonensis: Role of the PKR/IFN1/IL-10 axis. Carolina Torturella Rath Laila Castro Schnellrath Clarissa R Damaso Luciana Barros de Arruda Pedro Fernando da Costa Vasconcelos Claudia Gomes Marcia Dalastra Laurenti Teresa Cristina Calegari Silva Áislan de Carvalho Vivarini Nicolas Fasel Renata Meirelles Santos Pereira Ulisses Gazos Lopes 2019-06-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0007500 https://doaj.org/article/9bcc055464d548a2afe91ed032f6c070 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0007500 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007500 https://doaj.org/article/9bcc055464d548a2afe91ed032f6c070 PLoS Neglected Tropical Diseases, Vol 13, Iss 6, p e0007500 (2019) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2019 ftdoajarticles https://doi.org/10.1371/journal.pntd.0007500 2022-12-31T09:15:21Z Background Leishmania parasites are transmitted to vertebrate hosts by phlebotomine sandflies and, in humans, may cause tegumentary or visceral leishmaniasis. The role of PKR (dsRNA activated kinase) and Toll-like receptor 3 (TLR3) activation in the control of Leishmania infection highlights the importance of the engagement of RNA sensors, which are usually involved in the antiviral cell response, in the fate of parasitism by Leishmania. We tested the hypothesis that Phlebovirus, a subgroup of the Bunyaviridae, transmitted by sandflies, would interfere with Leishmania infection. Methodology/principal findings We tested two Phlebovirus isolates, Icoaraci and Pacui, from the rodents Nectomys sp. and Oryzomys sp., respectively, both natural sylvatic reservoir of Leishmania (Leishmania) amazonensis from the Amazon region. Phlebovirus coinfection with L. (L.) amazonensis in murine macrophages led to increased intracellular growth of L. (L.) amazonensis. Further studies with Icoaraci coinfection revealed the requirement of the PKR/IFN1 axis on the exacerbation of the parasite infection. L. (L.) amazonensis and Phlebovirus coinfection potentiated PKR activation and synergistically induced the expression of IFNβ and IL-10. Importantly, in vivo coinfection of C57BL/6 mice corroborated the in vitro data. The exacerbation effect of RNA virus on parasite infection may be specific because coinfection with dengue virus (DENV2) exerted the opposite effect on parasite load. Conclusions Altogether, our data suggest that coinfections with specific RNA viruses shared by vectors or reservoirs of Leishmania may enhance and sustain the activation of host cellular RNA sensors, resulting in aggravation of the parasite infection. The present work highlights new perspectives for the investigation of antiviral pathways as important modulators of protozoan infections. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 13 6 e0007500 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Carolina Torturella Rath Laila Castro Schnellrath Clarissa R Damaso Luciana Barros de Arruda Pedro Fernando da Costa Vasconcelos Claudia Gomes Marcia Dalastra Laurenti Teresa Cristina Calegari Silva Áislan de Carvalho Vivarini Nicolas Fasel Renata Meirelles Santos Pereira Ulisses Gazos Lopes Amazonian Phlebovirus (Bunyaviridae) potentiates the infection of Leishmania (Leishmania) amazonensis: Role of the PKR/IFN1/IL-10 axis. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Background Leishmania parasites are transmitted to vertebrate hosts by phlebotomine sandflies and, in humans, may cause tegumentary or visceral leishmaniasis. The role of PKR (dsRNA activated kinase) and Toll-like receptor 3 (TLR3) activation in the control of Leishmania infection highlights the importance of the engagement of RNA sensors, which are usually involved in the antiviral cell response, in the fate of parasitism by Leishmania. We tested the hypothesis that Phlebovirus, a subgroup of the Bunyaviridae, transmitted by sandflies, would interfere with Leishmania infection. Methodology/principal findings We tested two Phlebovirus isolates, Icoaraci and Pacui, from the rodents Nectomys sp. and Oryzomys sp., respectively, both natural sylvatic reservoir of Leishmania (Leishmania) amazonensis from the Amazon region. Phlebovirus coinfection with L. (L.) amazonensis in murine macrophages led to increased intracellular growth of L. (L.) amazonensis. Further studies with Icoaraci coinfection revealed the requirement of the PKR/IFN1 axis on the exacerbation of the parasite infection. L. (L.) amazonensis and Phlebovirus coinfection potentiated PKR activation and synergistically induced the expression of IFNβ and IL-10. Importantly, in vivo coinfection of C57BL/6 mice corroborated the in vitro data. The exacerbation effect of RNA virus on parasite infection may be specific because coinfection with dengue virus (DENV2) exerted the opposite effect on parasite load. Conclusions Altogether, our data suggest that coinfections with specific RNA viruses shared by vectors or reservoirs of Leishmania may enhance and sustain the activation of host cellular RNA sensors, resulting in aggravation of the parasite infection. The present work highlights new perspectives for the investigation of antiviral pathways as important modulators of protozoan infections. |
format |
Article in Journal/Newspaper |
author |
Carolina Torturella Rath Laila Castro Schnellrath Clarissa R Damaso Luciana Barros de Arruda Pedro Fernando da Costa Vasconcelos Claudia Gomes Marcia Dalastra Laurenti Teresa Cristina Calegari Silva Áislan de Carvalho Vivarini Nicolas Fasel Renata Meirelles Santos Pereira Ulisses Gazos Lopes |
author_facet |
Carolina Torturella Rath Laila Castro Schnellrath Clarissa R Damaso Luciana Barros de Arruda Pedro Fernando da Costa Vasconcelos Claudia Gomes Marcia Dalastra Laurenti Teresa Cristina Calegari Silva Áislan de Carvalho Vivarini Nicolas Fasel Renata Meirelles Santos Pereira Ulisses Gazos Lopes |
author_sort |
Carolina Torturella Rath |
title |
Amazonian Phlebovirus (Bunyaviridae) potentiates the infection of Leishmania (Leishmania) amazonensis: Role of the PKR/IFN1/IL-10 axis. |
title_short |
Amazonian Phlebovirus (Bunyaviridae) potentiates the infection of Leishmania (Leishmania) amazonensis: Role of the PKR/IFN1/IL-10 axis. |
title_full |
Amazonian Phlebovirus (Bunyaviridae) potentiates the infection of Leishmania (Leishmania) amazonensis: Role of the PKR/IFN1/IL-10 axis. |
title_fullStr |
Amazonian Phlebovirus (Bunyaviridae) potentiates the infection of Leishmania (Leishmania) amazonensis: Role of the PKR/IFN1/IL-10 axis. |
title_full_unstemmed |
Amazonian Phlebovirus (Bunyaviridae) potentiates the infection of Leishmania (Leishmania) amazonensis: Role of the PKR/IFN1/IL-10 axis. |
title_sort |
amazonian phlebovirus (bunyaviridae) potentiates the infection of leishmania (leishmania) amazonensis: role of the pkr/ifn1/il-10 axis. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2019 |
url |
https://doi.org/10.1371/journal.pntd.0007500 https://doaj.org/article/9bcc055464d548a2afe91ed032f6c070 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 13, Iss 6, p e0007500 (2019) |
op_relation |
https://doi.org/10.1371/journal.pntd.0007500 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007500 https://doaj.org/article/9bcc055464d548a2afe91ed032f6c070 |
op_doi |
https://doi.org/10.1371/journal.pntd.0007500 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
13 |
container_issue |
6 |
container_start_page |
e0007500 |
_version_ |
1766343795801063424 |