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Despite the increasing number of studies concerning insect immunity,  Lutzomyia longipalpis  immune responses in the presence of  Leishmania infantum chagasi  infection has not been widely investigated. The few available studies analyzed the role of the Toll and IMD pathways involved in response against  Leishmania  and microbial infections. Nevertheless, effector molecules responsible for controlling sand fly infections have not been identified. In the present study we investigated the role a signal transduction pathway, the Transforming Growth Factor-beta (TGF-β) pathway, on the interrelation between  L. longipalpis  and  L. i. chagasi . We identified an  L. longipalpis  homolog belonging to the multifunctional cytokine TGF-β gene family ( LlTGF -β), which is closely related to the activin/inhibin subfamily and potentially involved in responses to infections. We investigated this gene expression through the insect development and in adult flies infected with  L. i. chagasi . Our results showed that  LlTGF -β was expressed in all  L. longipalpis  developmental stages and was upregulated at the third day post  L. i. chagasi  infection, when protein levels were also higher as compared to uninfected insects. At this point blood digestion is finished and parasites are in close contact with the insect gut. In addition, we investigated the role of LlTGF-β on  L. longipalpis  infection by  L. i. chagasi  using either gene silencing by RNAi or pathway inactivation by addition of the TGF-β receptor inhibitor SB431542. The blockage of the LlTGF-β pathway increased significantly antimicrobial peptides expression and nitric oxide levels in the insect gut, as expected. Both methods led to a decreased  L. i. chagasi  infection. Our results show that inactivation of the  L. longipalpis  TGF-β signal transduction pathway reduce  L. i. chagasi  survival, therefore suggesting that under natural conditions the parasite benefits from the insect LlTGF-β pathway, as already seen in  Plamodium  infection of mosquitoes.

Lutzomyia longipalpis TGF-β Has a Role in Leishmania infantum chagasi Survival in the Vector