Circulating Immune Cells Mediate a Systemic RNAi-Based Adaptive Antiviral Response in Drosophila

Publication date: 6 April 2017
Source:Cell, Volume 169, Issue 2
Author(s): Michel Tassetto, Mark Kunitomi, Raul Andino
Effective antiviral protection in multicellular organisms relies on both cell-autonomous and systemic immunity. Systemic immunity mediates the spread of antiviral signals from infection sites to distant uninfected tissues. In arthropods, RNA interference (RNAi) is responsible for antiviral defense. Here, we show that flies have a sophisticated systemic RNAi-based immunity mediated by macrophage-like haemocytes. Haemocytes take up dsRNA from infected cells and, through endogenous transposon reverse transcriptases, produce virus-derived complementary DNAs (vDNA). These vDNAs template de novo synthesis of secondary viral siRNAs (vsRNA), which are secreted in exosome-like vesicles. Strikingly, exosomes containing vsRNAs, purified from haemolymph of infected flies, confer passive protection against virus challenge in naive animals. Thus, similar to vertebrates, insects use immune cells to generate immunological memory in the form of stable vDNAs that generate systemic immunity, which is mediated by the vsRNA-containing exosomes.

Graphical abstract

Teaser

Drosophila, thought to lack an adaptive immune system, have dedicated immune cells that can alter their genetic repertoire to amplify and spread systemically antiviral RNAi signals to combat viral infection, providing protection to naive cells.


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