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

Cell Host Microbe. 2016 Sep 14;20(3):318-328. doi: 10.1016/j.chom.2016.08.001. Epub 2016 Sep 1.


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: Akt; Leishmania; Leishmania RNA virus; TLR-3; macrophage survival; miR-155.

MeSH terms

  • 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*


  • MicroRNAs
  • Mirn155 microRNA, mouse
  • TLR3 protein, mouse
  • Toll-Like Receptor 3
  • Proto-Oncogene Proteins c-akt