The role of midgut immunity and homeostasis in Leishmania survival, development, and transmission by the sand fly Lutzomyia longipalpis

Sand flies are hematophagous insects that feed on a wide range of mammalian hosts and vector Leishmania parasites.  Parasites undergo their development and proliferate exclusively within the midgut of the sand fly.  A crucial step in overcoming the insect defenses and becoming transmissible is attachment to the midgut epithelium.  It has been shown in mosquitoes that the microbial community residing in the midgut alters the immune response of the vector and can lower the vector competence.  Recently, a molecular connection between immunity, JAK/STAT, and EGFR signaling pathways have been established in Drosophila melanogaster.  Epithelium cells damaged by microbes and reactive oxygen species from the immune response secrete the ligand Upd3 to the visceral muscle cells of the midgut.  In turn muscle cells secrete the epidermal growth factor ligands Vein, Keren, and Spitz which are recognized by the EGF receptors of intestinal stem cells (ISCs) inducing their proliferation and differentiation leading to regeneration of the gut epithelium.  Here we provide preliminary evidence that microbes are able to modulate the immunity and gut renewal in the sand fly Lutzomyia longipalpis.  Our goal is to develop a novel paratransgenic approach to diminishing the vector competence of sand flies for Leishmania.