In recent years, Drosophila melanogaster has been set up as a host model system to study the immune response. Unlike higher vertebrates, Drosophila lacks an adaptive immune system but relies on innate immune signalling, such as the Toll pathway, as a significant microbial defence pathway against systemic infections. Recently, we reported trained immunity and a memory response in Drosophila against secondary bacterial infection. This memory response relies on circulating macrophage-like cells called hemocytes and their enhanced post-injury response. The Toll pathway was induced even by an aseptic injury on the thorax of Drosophila adults with an upregulation of defence-related genes like anti-microbial peptides (AMPs). In the absence of the Toll 1 receptor in hemocytes, both survival and immune memory post-injury or infection were compromised. The rise in intracellular hemocyte hydrogen peroxide acts as a DAMP signal at the injury site and elevates the upd3 cytokine and various AMP expressions via the draper/src42A/shark pathway. The prior injury conferred protection for up to 5 days in terms of survival against a secondary Enterococcus faecalis systemic infection by increasing secondary AMP levels. Flies that did not elevate intracellular ROS levels after an injury failed to show a heightened AMP activation to a secondary infection. In the current study, we intend to investigate the molecular basis of this immune activation and memory response against other bacterial and fungal pathogens. We will use comparative transcriptomics, monitor epigenetic changes in hemocytes post-injury and employ molecular genetics to unravel pathway activation implicated in immunological memory in insects.
