Functional characterization in the immunity of DNase II in Drosophila melanogaster

Abstract

DNases are enzymes that play a crucial role in degradation of DNA, essential for innate immune responses of mammals. While the biochemical properties of DNase II have been extensively elucidated in mammals, there is little characterization of its functional role in immunological mechanisms. DNases possess antimicrobial activity, and their absence causes susceptibility to infections, but the molecular pathways underlying this susceptibility are yet to be delineated. In DNase II null mutants we discovered that absence of DNase II causes accumulation of apoptotic DNA, developmental defects, increased susceptibility to infection and dysregulation of known immune pathways upon injury. We also further expand on the properties of this enzyme in insects with respect to its subcellular localisation and non-cell autonomous function. We tried to assess the humoral and cellular immune pathways that are classically associated with damage responses to understand the effects of DNA accumulation. In the DNase II mutant, hemocytes have regular phagocytic activity and there is no aberration in the JNK pathway, however, we noticed some discrepancies in the IMD pathway. We also tried identifying if a cytosolic sensor of DNA homologous to mammalian cGAS exists in flies and if accumulation of DNA has effects on the cGAS-STING pathway. Lastly, we also explored the role of another DNase, Stress Induced DNase and the possible synergy between SID and DNase II.