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Background  Sand flies are the vectors of  Leishmania  parasites. To develop in the sand fly midgut,  Leishmania  multiplies and undergoes various stage differentiations giving rise to the infective form, the metacyclic promastigotes. To determine the changes in sand fly midgut gene expression caused by the presence of  Leishmania , we performed RNA-Seq of uninfected and  Leishmania infantum -infected  Lutzomyia longipalpis  midguts from seven different libraries corresponding to time points which cover the various  Leishmania  developmental stages.    Results  The combined transcriptomes resulted in the de novo assembly of 13,841 sand fly midgut transcripts. Importantly, only 113 sand fly transcripts, about 1%, were differentially expressed in the presence of  Leishmania  parasites. Further, we observed distinct differentially expressed sand fly midgut transcripts corresponding to the presence of each of the various  Leishmania  stages suggesting that each parasite stage influences midgut gene expression in a specific manner. Two main patterns of sand fly gene expression modulation were noted. At early time points (days 1–4), more transcripts were down-regulated by  Leishmania  infection at large fold changes (> 32 fold). Among the down-regulated genes, the transcription factor Forkhead/HNF-3 and hormone degradation enzymes were differentially regulated on day 2 and appear to be the upstream regulators of nutrient transport, digestive enzymes, and peritrophic matrix proteins. Conversely, at later time points (days 6 onwards), most of the differentially expressed transcripts were up-regulated by  Leishmania  infection with small fold changes (< 32 fold). The molecular functions of these genes have been associated with the metabolism of lipids and detoxification of xenobiotics.    Conclusion  Overall, our data suggest that the presence of  Leishmania  produces a limited change in the midgut transcript expression profile in sand flies. Further,  Leishmania  modulates sand fly gene expression early on in the developmental cycle in order to overcome the barriers imposed by the midgut, yet it behaves like a commensal at later time points where a massive number of parasites in the anterior midgut results only in modest changes in midgut gene expression.

Leishmania infection induces a limited differential gene expression in the sand fly midgut