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