The Drosophila larva as a tool to study gut-associated macrophages: PI3K regulates a discrete hemocyte population at the proventriculus.

Immune cells not only patrol the body in the circulation but also importantly, associate with specific tissues, such as the intestinal epithelium. The complex interactions between immune cells and their target tissues are difficult to study and simple, genetically tractable models are lacking. Here, we present the first thorough characterization of gut-associated macrophages in Drosophila larvae. We analyze their gene expression, morphology, development and lineage and importantly, demonstrate that they are functional (phagocytic) macrophages. We test their regulation by phosphoinositide 3-kinase (PI3K) and show evidence that this pathway regulates the population size of gut hemocytes and their phagocytic activity, reminiscent of recent findings in mammalian colitis models. Our data suggest that PI3K signaling modifies the adhesive properties of hemocytes, a possible mechanism for gut-hemocyte regulation. These results demonstrate the potential of the Drosophila larva as a simple tool to uncover mechanisms regulating recruitment and maintenance of innate immune cells at their target tissues.