Abstract

Palladacycle complex DPPE 1.2 was previously reported to inhibit the in vitro and in vivo infection by Leishmania (Leishmania) amazonensis. The aim of the present study was to compare the effect of DPPE 1.2, in association with heat-killed Propionibacterium acnes, on L. (L.) amazonensis infection in two mouse strains, BALB/c and C57BL/6, and to evaluate the immune responses of the treated animals. Foot lesions of L. (L.) amazonensis-infected mice were injected with DPPE 1.2 alone, or associated with P. acnes as an adjuvant. Analysis of T-cell populations in the treated mice and in untreated controls was performed by FACS. Detection of IFN-γ-secreting lymphocytes was carried out by an ELISPOT assay and active TGF-β was measured by means of a double-sandwich ELISA test. The treatment with DPPE 1.2 resulted in a significant reduction of foot lesion sizes and parasite burdens in both mouse strains, and the lowest parasite burden was found in mice treated with DPPE 1.2 plus P. acnes. Mice treated with DPPE 1.2 alone displayed a significant increase of TCD4+ and TCD8+ lymphocytes and IFN-γ secretion which were significantly higher in animals treated with DPPE 1.2 plus P. acnes. A significant reduction of active TGF-β was observed in mice treated with DPPE 1.2 alone or associated with P. acnes. Moreover, DPPE 1.2 associated to P. acnes was non-toxic to treated animals. The destruction of L. (L.) amazonensis by DPPE 1.2 was followed by host inflammatory responses which were exacerbated when the palladacycle complex was associated with P. acnes.

Highlights

  • Parasites belonging to the Leishmania genus are etiological agents of cutaneous, mucocutaneous, and visceral diseases in humans and mammals

  • All animals from both strains treated with DPPE 1.2 displayed a significant reduction of parasite load and this reduction was significantly higher in mice treated with DPPE 1.2 plus P. acnes

  • The treatment with DPPE 1.2 resulted in a twofold higher reduction of parasite load in C57BL/6 mice compared to that observed in BALB/c strain, while this difference was of 600-fold between the two strains treated with DPPE 1.2 plus P. acnes

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Summary

Introduction

Parasites belonging to the Leishmania genus are etiological agents of cutaneous, mucocutaneous, and visceral diseases in humans and mammals. Miltefosine showed a high efficacy for treatment of visceral leishmaniasis in India and of cutaneous leishmaniasis in Colombia, (Sundar et al, 2002; Soto et al, 2004) but its use is limited by host teratogenicity and development of parasite resistance (Croft and Coombs, 2003). The development of new leishmanicidal drugs continues to be a priority for the control of leishmaniasis and several compounds including synthetic and natural products extracted from plants and marine sources have exhibited different degrees of efficacy in the treatment of experimental leishmaniasis (Sen and Chatterjee, 2011; Tempone et al, 2011; Coa et al, 2015; Ortiz et al, 2016; Acevedo et al, 2017)

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