Melittin induces in vitro death of Leishmania (Leishmania) infantum by triggering the cellular innate immune response
Andreia Vieira Pereira1 , Gustavo de Barros1 , Erika Gracielle Pinto2,3, Andre Gustavo Tempone2 , Ricardo de Oliveira Orsi4,5, Lucilene Delazari dos Santos1,5, Sueli Calvi1,5, Rui Seabra Ferreira Jr1,5, Daniel Carvalho Pimenta6 and Benedito Barraviera1,5* [ + show more ]
Received: 7 August 2015 | Accepted: 4 January 2016 | Published: 8 January 2016
https://doi.org/10.1186/s40409-016-0055-x
Abstract
Background: Apis mellifera venom, which has already been recommended as an alternative anti-inflammatory treatment, may be also considered an important source of candidate molecules for biotechnological and biomedical uses, such as the treatment of parasitic diseases. Methods: Africanized honeybee venom from Apis mellifera was fractionated by RP-C18-HPLC and the obtained melittin was incubated with promastigotes and intracellular amastigotes of Leishmania (L.) infantum. Cytotoxicity to mice peritoneal macrophages was evaluated through mitochondrial oxidative activity. The production of anti- and pro-inflammatory cytokines, NO and H2O2 by macrophages was determined. Results: Promastigotes and intracellular amastigotes were susceptible to melittin (IC50 28.3 μg.mL−1 and 1.4 μg.mL−1 , respectively), but also showed mammalian cell cytotoxicity with an IC50 value of 5.7 μg.mL−1 . Uninfected macrophages treated with melittin increased the production of IL-10, TNF-α, NO and H2O2. Infected melittin-treated macrophages increased IL-12 production, but decreased the levels of IL-10, TNF-α, NO and H2O2. Conclusions: The results showed that melittin acts in vitro against promastigotes and intracellular amastigotes of Leishmania (L.) infantum. Furthermore, they can act indirectly on intracellular amastigotes through a macrophage immunomodulatory effect.
Keywords: Melittin, Apis mellifera, Leishmania, Leishmaniasis, Peptides, Toxins, Antiparasitic, Cytokines