Abstract
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.
Highlights
Leishmaniasis is a serious public health concern, affecting millions of people every year
Sequences obtained from organisms of different taxa but belonging to the same TGF-β subfamily were grouped such as activin/inhibin, TGF-β sensu stricto, and glass bottom boat (GBB) member of the bone morphogenic protein (BMP) subfamily (Figure 1)
TGF-β belongs to a family of multifunctional cytokines found in organisms that go from arthropods to mammals (Massague, 1990)
Summary
Leishmaniasis is a serious public health concern, affecting millions of people every year. Leishmaniasis is caused by parasites from the genus Leishmania. These parasites are transmitted in the New and Old World by phlebotomine sand flies belonging to the Lutzomyia and Phlebotomus genera, respectively. When a female sand fly feeds on an infected vertebrate host, TGF-β and Lutzomyia Longipalpis Immunity macrophages containing amastigote parasites are ingested. The aflagellated immotile rounded parasites transform into flagellated motile promastigotes that multiply and migrate to the anterior midgut (Lainson and Rangel, 2005). Parasites secrete a chitinolytic enzyme that attack and damage the sand fly stomodeal valve, leading to the regurgitation of the gut content at the bite site (Rogers et al, 2008). The intricate interactions among Leishmania parasites, gut microbioma and the insect immunity are complex, and evolved to avoid the harmful consequences of an eventual uncontrolled microbial or leishmanial growth inside the insect gut (Sant’Anna et al, 2014; Kelly et al, 2017; Telleria et al, 2018)
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