Microbial Ecology and Epithelial Immunity of Lutzomyia longipalpis
Sand fly larvae develop in decaying organic substrates such as rodent feces. This strongly suggests a close association between sand flies and bacteria. It has been shown by a culturing approach that sand fly adults carry in the midgut a large, diverse bacterial community. Some bacteria, such as Serratia marcescens, can directly inhibit Leishmania development in vitro. However, nothing is known about the role of bacteria in: a) sand fly larval development, b) midgut colonization of adult flies, c) maturation of innate epithelial immunity and epithelial renewal, and consequently d) vector competence of sand flies for Leishmania. This project is the first to comprehensively study the tripartite interactions among sand fly - bacteria - Leishmania from perspectives of larval development, midgut epithelial biology, and vector competence for Leishmania parasites.
In this project, we will investigate how sand flies, Lutzomyia longipalpis, regulate the gut commensal microbial community and maintain midgut microbial and immune homeostasis. Furthermore, we will study the effects of the microbiota on the sand fly midgut epithelium (immunity, regeneration) and consequent vector capacity of this insect for Leishmania parasites. The overall long-term goal of this research is to generate sand flies with the midgut refractory to Leishmania parasites based on the modified midgut microbial community (paratransgenesis) and/or up-regulation of specific innate epithelial immunity gene(s).