Purpose Sand flies are the only proven vectors of leishmaniases, a tropical neglected disease endemic in at least 92 countries. Vector-parasite interactions play a significant role in vector-borne disease transmission. There are various bottlenecks to Leishmania colonization of the sand fly midgut. Such bottlenecks include the production of innate immune-related molecules, digestive proteases, parasite impermeable peritrophic membrane, and resident gut microbiota. These barriers determine the parasite load transmitted and, consequently, the disease outcome in mammalian host. Therefore, it is important to understand the molecular responses of both sand fly and Leishmania during infection. Method Here, we reviewed the published literature on sand fly-Leishmania interactions bringing together earlier and current findings to highlight new developments and research gaps in the field. Conclusion Recent research studies on sand fly-Leishmania interaction have revealed contrasting observations to past studies. However, how Leishmania parasites evade the sand fly immune response still needs further research. Sand fly response to Leishmania infection can be best understood by analyzing its tissue transcriptome. Better characterization of the role of midgut components could be a game changer in development of transmission-blocking strategies for leishmaniasis.
