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

Abstract

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.

Non-immune Traits Triggered by Blood Intake Impact Vectorial Competence

“…Maintaining the redox balance would be beneficial for viruses as it would protect them from oxidative damage. However, the relevance of these changes to the course of viral infection has not been experimentally addressed in the literature yet, despite alterations in expression of metabolic enzymes being regularly observed in transcriptomic analyses of infected vector digestive apparatus ( Padrón et al, 2014 ; Angleró-Rodríguez et al, 2017a ; Etebari et al, 2017 ; Narasimhan et al, 2017 ; Coutinho-Abreu et al, 2020 ). A large amount of gene expression data on vector infection has now accumulated, and it could be used to direct studies focusing on the crosstalk between canonical immunity pathways and carbohydrate/energy metabolism, the so-called immunometabolism, and the relevance of them to vector biology ( Samaddar et al, 2020 ).…”