Mammalian Innate Immune Response to a Leishmania-Resident RNA Virus Increases Macrophage Survival to Promote Parasite Persistence.

Details

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State: Public
Version: Author's accepted manuscript
Serval ID
serval:BIB_58680551DAFF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Mammalian Innate Immune Response to a Leishmania-Resident RNA Virus Increases Macrophage Survival to Promote Parasite Persistence.
Journal
Cell host & microbe
Author(s)
Eren R.O., Reverte M., Rossi M., Hartley M.A., Castiglioni P., Prevel F., Martin R., Desponds C., Lye L.F., Drexler S.K., Reith W., Beverley S.M., Ronet C., Fasel N.
ISSN
1934-6069 (Electronic)
ISSN-L
1931-3128
Publication state
Published
Issued date
14/09/2016
Peer-reviewed
Oui
Volume
20
Number
3
Pages
318-328
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Some strains of the protozoan parasite Leishmania guyanensis (L.g) harbor a viral endosymbiont called Leishmania RNA virus 1 (LRV1). LRV1 recognition by TLR-3 increases parasite burden and lesion swelling in vivo. However, the mechanisms by which anti-viral innate immune responses affect parasitic infection are largely unknown. Upon investigating the mammalian host's response to LRV1, we found that miR-155 was singularly and strongly upregulated in macrophages infected with LRV1+ L.g when compared to LRV1- L.g. LRV1-driven miR-155 expression was dependent on TLR-3/TRIF signaling. Furthermore, LRV1-induced TLR-3 activation promoted parasite persistence by enhancing macrophage survival through Akt activation in a manner partially dependent on miR-155. Pharmacological inhibition of Akt resulted in a decrease in LRV1-mediated macrophage survival and consequently decreased parasite persistence. Consistent with these data, miR-155-deficient mice showed a drastic decrease in LRV1-induced disease severity, and lesional macrophages from these mice displayed reduced levels of Akt phosphorylation.

Keywords
Animals, Cell Survival, Disease Models, Animal, Immunity, Innate, Leishmania guyanensis/pathogenicity, Leishmania guyanensis/physiology, Leishmania guyanensis/virology, Leishmaniasis, Mucocutaneous/parasitology, Leishmaniasis, Mucocutaneous/pathology, Leishmaniavirus/immunology, Macrophages/immunology, Macrophages/parasitology, Mice, Mice, Knockout, MicroRNAs/metabolism, Proto-Oncogene Proteins c-akt/metabolism, Toll-Like Receptor 3/metabolism, Akt, Leishmania, Leishmania RNA virus, TLR-3, macrophage survival, miR-155
Pubmed
Web of science
Create date
14/09/2016 8:11
Last modification date
20/08/2019 14:12
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