Amazonian Phlebovirus (Bunyaviridae) potentiates the infection of Leishmania (Leishmania) amazonensis: Role of the PKR/IFN1/IL-10 axis.

Details

Serval ID
serval:BIB_75870B3A26CF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Amazonian Phlebovirus (Bunyaviridae) potentiates the infection of Leishmania (Leishmania) amazonensis: Role of the PKR/IFN1/IL-10 axis.
Journal
PLoS neglected tropical diseases
Author(s)
Rath C.T., Schnellrath L.C., Damaso C.R., de Arruda L.B., Vasconcelos PFDC, Gomes C., Laurenti M.D., Calegari Silva T.C., Vivarini Á.C., Fasel N., Pereira RMS, Lopes U.G.
ISSN
1935-2735 (Electronic)
ISSN-L
1935-2727
Publication state
Published
Issued date
06/2019
Peer-reviewed
Oui
Volume
13
Number
6
Pages
e0007500
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
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.
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.
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.
Keywords
Animals, Bunyaviridae Infections/complications, Cells, Cultured, Coinfection/immunology, Disease Models, Animal, Disease Susceptibility, Interferon-beta/metabolism, Interleukin-10/metabolism, Leishmania/immunology, Leishmaniasis/immunology, Mice, Inbred C57BL, Models, Theoretical, Phlebovirus/immunology, eIF-2 Kinase/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
24/06/2019 17:08
Last modification date
16/12/2019 7:19
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