Mixed Formulation of Conventional and Pegylated Meglumine Antimoniate-Containing Liposomes Reduces Inflammatory Process and Parasite Burden in Leishmania infantum-Infected BALB/c Mice

Reis, Levi Eduardo Soares; Brito, Rory Cristiane Fortes de; Cardoso, Jamille Mirelle de Oliveira; Mathias, Fernando Augusto Siqueira; Aguiar-Soares, Rodrigo Dian de Oliveira; Carneiro, Cláudia Martins; Vieira, Paula Melo de Abreu; Ramos, Guilherme Santos; Frézard, Frédéric; Roatt, Bruno Mendes; Reis, Alexandre Barbosa

doi:10.1128/aac.00962-17

Cited by 19 publications

(13 citation statements)

References 38 publications

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“…Secondly, it could also be due to the use of liposomes, as empty liposomes reduced the formation of granulomas. A recent study reported that the use of liposomal formulations of meglumine antimoniate was associated with a reduced hepatic tissue response and increased Th1 response [50], which is consistent with the slightly lower granulomatous response observed in mice treated with L-Galf compared to Galf in the present study.…”

Section: Discussionsupporting

confidence: 92%

In vitro and in vivo immunomodulatory properties of octyl-β-d-galactofuranoside during Leishmania donovani infection

et al. 2019

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BackgroundThe chemotherapeutic arsenal available to treat visceral leishmaniasis is currently limited, in view of many drawbacks such as high cost, toxicity or emerging resistance. New therapeutic strategies are particularly needed to improve the management and the outcome in immunosuppressed patients. The combination of an immunomodulatory drug to a conventional anti-Leishmania treatment is an emerging concept to reverse the immune bias from Th2 to Th1 response to boost healing and prevent relapses.MethodsHere, immunostimulating and leishmanicidal properties of octyl-β-d-galactofuranose (Galf) were assessed in human monocyte-derived macrophages (HM) and in a murine model, after challenge with Leishmania donovani promastigotes. We recorded parasite loads and expression of various cytokines and immune effectors in HM and mouse organs (liver, spleen, bone marrow), following treatment with free (Galf) and liposomal (L-Galf) formulations.ResultsBoth treatments significantly reduced parasite proliferation in HM, as well as liver parasite burden in vivo (Galf, P < 0.05). Consistent with in vitro results, we showed that Galf- and L-Galf-treated mice displayed an enhanced Th1 immune response, particularly in the spleen where pro-inflammatory cytokines TNF-α, IL-1β and IL-12 were significantly overexpressed compared to control group. The hepatic recruitment of myeloid cells was also favored by L-Galf treatment as evidenced by the five-fold increase of myeloperoxidase (MPO) induction, which was associated with a higher number of MPO-positive cells within granulomas. By contrast, the systemic level of various cytokines such as IL-1β, IL-6, IL-17A or IL-27 was drastically reduced at the end of treatment.ConclusionsOverall, these results suggest that Galf could be tested as an adjuvant in combination with current anti-parasitic drugs, to restore an efficient immune response against infection in a model of immunosuppressed mice.

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Section: Discussionsupporting

confidence: 92%

In vitro and in vivo immunomodulatory properties of octyl-β-d-galactofuranoside during Leishmania donovani infection

et al. 2019

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“…Parasite burden in the spleen was analyzed 30 days after infection by real-time PCR (qPCR) quantification, as described by [ 30 ]. Briefly, at the end of the study, the mice were euthanized, and the spleens were extracted and used for genomic DNA isolation with the CTAB reagent.…”

Section: Methodsmentioning

confidence: 99%

Chimeric Vaccines Designed by Immunoinformatics-Activated Polyfunctional and Memory T Cells That Trigger Protection against Experimental Visceral Leishmaniasis

et al. 2020

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Many vaccine candidates against visceral leishmaniasis (VL) have been proposed; however, to date, none of them have been efficacious for the human or canine disease. On this basis, the design of leishmaniasis vaccines has been constantly changing, and the use of approaches to select specific epitopes seems to be crucial in this scenario. The ability to predict T cell-specific epitopes makes immunoinformatics an even more necessary approach, as in VL an efficient immune response against the parasite is triggered by T lymphocytes in response to Leishmania spp. immunogenic antigens. Moreover, the success of vaccines depends on the capacity to generate long-lasting memory and polyfunctional cells that are able to eliminate the parasite. In this sense, our study used a combination of different approaches to develop potential chimera candidate vaccines against VL. The first point was to identify the most immunogenic epitopes of Leishmania infantum proteins and construct chimeras composed of Major histocompatibility complex (MHC) class I and II epitopes. For this, we used immunoinformatics features. Following this, we validated these chimeras in a murine model in a thorough memory study and multifunctionality of T cells that contribute to a better elucidation of the immunological protective mechanisms of polyepitope vaccines (chimera A and B) using multicolor flow cytometry. Our results showed that in silico-designed chimeras can elicit polyfunctional T cells producing T helper (Th)1 cytokines, a strong immune response against Leishmania antigen, and the generation of central and effector memory T cells in the spleen cells of vaccinated animals that was able to reduce the parasite burden in this organ. These findings contribute two potential candidate vaccines against VL that can be used in further studies, and help in this complex field of vaccine development against this challenging parasite.

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“…(Fajardo et al 2016) but it seems to be successful for Leishmania species. Reports of infection of dogs (Roatt et al 2012), hamsters (Moreira et al 2012b), mice (Reis et al 2017), and sand flies (Agrela and Feliciangeli 2015) demonstrate the potential use of this medium concerning in vivo Leishmania infection.…”

Section: Discussionmentioning

confidence: 94%

Liver infusion tryptose (LIT): the best choice for growth, viability, and infectivity of Leishmania infantum parasites

et al. 2020

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Leishmania spp. parasites have a complex biological cycle presenting basically two different morphological stages, the amastigote and promastigote forms. In vitro cultivation allows a more complete study of the biological aspects of these parasites, indicating better conditions for infection, immunoassay tests, drug evaluations, and vaccines. Thus, we evaluated the three most used culture media for Leishmania spp., Grace's insect cell culture medium (Grace's), liver infusion tryptose (LIT), and Schneider's insect medium (Schneider's), without supplementation or supplemented with fetal calf serum (FCS) and bovine serum albumin (Albumin) to evaluate the growth, viability, and infectivity of the L. infantum promastigotes. It was observed that promastigote forms have a better growth in LIT and Schneider's with or without FCS when compared to that in Grace's. The supplementation with albumin promoted greater viability of the parasites independent of the medium. For in vitro infection of J774.A1 macrophages using light microscopy and flow cytometry analyses, FCS-supplemented LIT and Grace's promoted higher percentage of infected macrophages and parasite load compared with Schneider's media. Taken together, our results demonstrated that the supplementation of LIT culture medium with FCS is the most suitable strategy to cultivate Leishmania infantum parasites enabling the maintenance of growth and infective parasites for research uses.

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Mixed Formulation of Conventional and Pegylated Meglumine Antimoniate-Containing Liposomes Reduces Inflammatory Process and Parasite Burden in Leishmania infantum-Infected BALB/c Mice

Cited by 19 publications

References 38 publications

In vitro and in vivo immunomodulatory properties of octyl-β-d-galactofuranoside during Leishmania donovani infection

In vitro and in vivo immunomodulatory properties of octyl-β-d-galactofuranoside during Leishmania donovani infection

Chimeric Vaccines Designed by Immunoinformatics-Activated Polyfunctional and Memory T Cells That Trigger Protection against Experimental Visceral Leishmaniasis

Liver infusion tryptose (LIT): the best choice for growth, viability, and infectivity of Leishmania infantum parasites

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