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

Remzi Onur Eren, Marta Reverte, Matteo Rossi, Mary Anne Hartley, Patrik Castiglioni, Florence Prevel, Ricardo Martin, Chantal Desponds, Lon Fye Lye, Stefan K. Drexler, Walter Reith, Stephen M. Beverley, Catherine Ronet, Nicolas Fasel

Research output: Contribution to journalArticle

18 Scopus citations

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.

Original languageEnglish
Pages (from-to)318-328
Number of pages11
JournalCell Host and Microbe
Volume20
Issue number3
DOIs
StatePublished - Sep 14 2016

Keywords

  • Akt
  • Leishmania
  • Leishmania RNA virus
  • TLR-3
  • macrophage survival
  • miR-155

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    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. (2016). Mammalian Innate Immune Response to a Leishmania-Resident RNA Virus Increases Macrophage Survival to Promote Parasite Persistence. Cell Host and Microbe, 20(3), 318-328. https://doi.org/10.1016/j.chom.2016.08.001