Retracing the horizontal transfer of a novel innate immune factor inDrosophila

Abstract

SummaryImmune systems are among the most dynamically evolving traits across the tree of life, and long-lived macroparasites play an outsized role in shaping animal immunity. Even without adaptive immunity, insects have evolved potent innate immune strategies to neutralize such enemies, including nematodes and parasitoid wasps. One such strategy relies on endosymbioses between insects and toxin-expressing bacteria. Here, we use genome editing inDrosophila melanogasterto retrace the evolution of two of such toxins —cytolethal distending toxin B(cdtB) andapoptosis inducing protein of 56kDa(aip56) — that were horizontally transferred from bacteriophages to insects. We found that acdtB::aip56fusion gene (fusionB), which is conserved inDrosophila ananassaesubgroup species, dramatically promoted fly survival and suppressed wasp development when expressed inD. melanogasterimmune tissues. FusionB, a functional nuclease, was secreted into the host hemolymph where it targeted the parasitoid embryo’s serosal tissue and is to our knowledge the first humoral anti-parasitoid toxin inDrosophila. When expressed ubiquitously,fusionBslowed development in late stage fly larvae and eventually killed flies, pointing to the salience of regulatory constraint in preventing autoimmunity. Our findings demonstrate how horizontal gene transfer, in the right regulatory context, can instantly provide new and potent innate immune modules in animals.