Abstract
BackgroundThe leishmaniases are important neglected diseases caused by Leishmania spp. which are transmitted by sand flies, Lutzomyia longipalpis being the main vector of visceral leishmaniasis in the Americas. The methodologies for leishmaniasis control are not efficient, causing 1.5 million reported cases annually worldwide, therefore showing the need for development of novel strategies and interventions to control transmission of the disease. The bacterium Wolbachia pipientis is being used to control viruses transmitted by mosquitoes, such as dengue and Zika, and its introduction in disease vectors has been effective against parasites such as Plasmodium. Here we show the first successful establishment of Wolbachia into two different embryonic cell lines from L. longipalpis, LL-5 and Lulo, and analysed its effects on the sand fly innate immune system, followed by in vitro Leishmania infantum interaction.ResultsOur results show that LL-5 cells respond to wMel and wMelPop-CLA strains within the first 72 h post-infection, through the expression of antimicrobial peptides and inducible nitric oxide synthase resulting in a decrease of Wolbachia detection in the early stages of infection. In subsequent passages, the wMel strain was not able to infect any of the sand fly cell lines while the wMelPop-CLA strain was able to stably infect Lulo cells and LL-5 at lower levels. In Wolbachia stably infected cells, the expression of immune-related genes involved with downregulation of the IMD, Toll and Jak-Stat innate immune pathways was significantly decreased, in comparison with the uninfected control, suggesting immune activation upon Wolbachia transinfection. Furthermore, Wolbachia transinfection did not promote a negative effect on parasite load in those cells.ConclusionsInitial strong immune responses of LL5 cells might explain the inefficiency of stable infections in these cells while we found that Lulo cells are more permissive to infection with Wolbachia causing an effect on the cell immune system, but not against in vitro L. infantum interaction. This establishes Lulo cells as a good system for the adaptation of Wolbachia in L. longipalpis.
Highlights
The leishmaniases are important neglected diseases caused by Leishmania spp. which are transmitted by sand flies, Lutzomyia longipalpis being the main vector of visceral leishmaniasis in the Americas
Wolbachia establishment into L. longipalpis cell lines The response of L. longipalpis LL-5 cells against infection with Wolbachia strains wMel and wMelPop-CLA was analysed at early stages of interaction for the first 72 h post-infection with the bacteria
When compared to the non-infected control group, LL-5 cells responded to wMel increasing the expression of the transcription factors at 12 h post-infection to Dorsal and at 24 h to STAT, while for wMelPop, the cells responded to Dorsal and Relish both at 12 h post-infection (Fig. 1c, e, g)
Summary
The leishmaniases are important neglected diseases caused by Leishmania spp. which are transmitted by sand flies, Lutzomyia longipalpis being the main vector of visceral leishmaniasis in the Americas. The endosymbiont bacterium Wolbachia has been used as an alternative strategy to control vectorborne diseases, through the reduction or blocking of pathogen infections. Different strains of this bacterium were introduced into mosquitoes, upregulating immune related genes, such as TEP1, Myd, SOCS36E, Cactus and the AMPs Defensin and Cepropin. This led to the reduction of infection by pathogens that cause different diseases such as dengue, chikungunya, malaria and Zika [15,16,17,18,19,20,21,22]
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