Dynamic of the Cellular Immune Response at the Dermal Site ofLeishmania (L.) amazonensisandLeishmania (V.) braziliensisInfection inSapajus apellaPrimate

Laurenti, Márcia Dalastra; Passero, Luiz Felipe Domingues; Tomokane, Thaíse Yumie; Francesquini, Fernanda de Camargo; Rocha, Mussya Cisotto; Gomes, Cláudia Maria de Castro; Corbett, Carlos Eduardo Pereira; Sílveira, Fernando Tobias

doi:10.1155/2014/134236

Cited by 15 publications

(11 citation statements)

References 25 publications

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“…In addition to the limiting-dilution assay, parasitism in the spleen and liver was evaluated by immunohistochemistry according to Laurenti and collaborators (Laurenti et al., 2014). Briefly, slides with histological sections were deparaffinized and hydrated.…”

Section: Methodsmentioning

confidence: 99%

Therapeutic effect of ursolic acid in experimental visceral leishmaniasis

Jesus

Fragoso

Yamamoto

et al. 2017

International Journal for Parasitology: Drugs and Drug Resistan

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Leishmaniasis is an important neglected tropical disease, affecting more than 12 million people worldwide. The available treatments are not well tolerated and present diverse side effects in patients, justifying the search for new therapeutic compounds. In the present study, the therapeutic potential and toxicity of ursolic acid (UA), isolated from the leaves of Baccharis uncinella C. DC. (Asteraceae), were evaluated in experimental visceral leishmaniasis. To evaluate the therapeutic potential of UA, hamsters infected with L. (L.) infantum were treated daily during 15 days with 1.0 or 2.0 mg UA/kg body weight, or with 5.0 mg amphotericin B/kg body weight by intraperitoneal route. Fifteen days after the last dose, the parasitism of the spleen and liver was stimated and the main histopathological alterations were recorded. The proliferation of splenic mononuclear cells was evaluated and IFN-γ, IL-4, and IL-10 gene expressions were analyzed in spleen fragments. The toxicity of UA and amphotericin B were evaluated in healthy golden hamsters by histological analysis and biochemical parameters. Animals treated with UA had less parasites in the spleen and liver when compared with the infected control group, and they also showed preservation of white and red pulps, which correlate with a high rate of proliferation of splenic mononuclear cells, IFN-γ mRNA and iNOS production. Moreover, animals treated with UA did not present alterations in the levels of AST, ALT, creatinine and urea. Taken together, these findings indicate that UA is an interesting natural compound that should be considered for the development of prototype drugs against visceral leishmaniasis.

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Section: Methodsmentioning

confidence: 99%

Therapeutic effect of ursolic acid in experimental visceral leishmaniasis

Jesus

Fragoso

Yamamoto

et al. 2017

International Journal for Parasitology: Drugs and Drug Resistan

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“…(L . ) amazonensis infection [ 54 , 55 , 56 ]. In addition, NO can be triggered by different stimuli as well as natural compounds from plants [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

The Effect of Ursolic Acid on Leishmania (Leishmania) amazonensis Is Related to Programed Cell Death and Presents Therapeutic Potential in Experimental Cutaneous Leishmaniasis

et al. 2015

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Among neglected tropical diseases, leishmaniasis is one of the most important ones, affecting more than 12 million people worldwide. The available treatments are not well tolerated, and present diverse side effects, justifying the search for new therapeutic compounds. In the present study, the activity of ursolic acid (UA) and oleanolic acid (OA) were assayed in experimental cutaneous leishmaniasis (in vitro and in vivo). Promastigote forms of L. amazonensis were incubated with OA and UA for 24h, and effective concentration 50% (EC50) was estimated. Ultraestructural alterations in Leishmania amazonensis promastigotes after UA treatment were evaluated by transmission electron microscopy, and the possible mode of action was assayed through Annexin V and propidium iodide staining, caspase 3/7 activity, DNA fragmentation and transmembrane mitochondrial potential. The UA potential was evaluated in intracellular amastigotes, and its therapeutic potential was evaluated in L. amazonensis infected BALB/c mice. UA eliminated L. amazonensis promastigotes with an EC50 of 6.4 μg/mL, comparable with miltefosine, while OA presented only a marginal effect on promastigote forms at 100 μg/mL. The possible mechanism by which promastigotes were eliminated by UA was programmed cell death, independent of caspase 3/7, but it was highly dependent on mitochondria activity. UA was not toxic for peritoneal macrophages from BALB/c mice, and it was able to eliminate intracellular amastigotes, associated with nitric oxide (NO) production. OA did not eliminate amastigotes nor trigger NO. L. amazonensis infected BALB/c mice submitted to UA treatment presented lesser lesion size and parasitism compared to control. This study showed, for the first time, that UA eliminate promastigote forms through a mechanism associated with programed cell death, and importantly, was effective in vivo. Therefore, UA can be considered an interesting candidate for future tests as a prototype drug for the treatment of cutaneous leishmaniasis.

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“…To evaluate the amastigote, IFNβ + , IL-10 + and iNOS + cells density, ten fields for each histological section were photographed with a 40X objective, and the number of immunostained amastigotes was quantified using Axiovision 4.0 software on a computer coupled to an optical microscope (Axioskop 2 plus; Carl-Zeiss, Jena, Germany). Subsequently, the density of immunostained parasites was calculated by determining the average number of amastigotes per mm 2 [32]. Quantitative analysis of reactive cells positive for IFNβ, IL-10 and iNOS was achieved through the processing of selected optical fields by Axioplan 2 Plus software (Carl Zeiss, Oberkochen, Germany).…”

Section: Methodsmentioning

confidence: 99%

Amazonian Phlebovirus (Bunyaviridae) potentiates the infection of Leishmania (Leishmania) amazonensis: Role of the PKR/IFN1/IL-10 axis

et al. 2019

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Background Leishmania parasites are transmitted to vertebrate hosts by phlebotomine sandflies and, in humans, may cause tegumentary or visceral leishmaniasis. The role of PKR (dsRNA activated kinase) and Toll-like receptor 3 (TLR3) activation in the control of Leishmania infection highlights the importance of the engagement of RNA sensors, which are usually involved in the antiviral cell response, in the fate of parasitism by Leishmania . We tested the hypothesis that Phlebovirus , a subgroup of the Bunyaviridae , transmitted by sandflies, would interfere with Leishmania infection. Methodology/Principal findings We tested two Phlebovirus isolates, Icoaraci and Pacui, from the rodents Nectomys sp. and Oryzomys sp ., respectively, both natural sylvatic reservoir of Leishmania (Leishmania) amazonensis from the Amazon region. Phlebovirus coinfection with L . (L . ) amazonensis in murine macrophages led to increased intracellular growth of L . (L . ) amazonensis . Further studies with Icoaraci coinfection revealed the requirement of the PKR/IFN1 axis on the exacerbation of the parasite infection. L . (L . ) amazonensis and Phlebovirus coinfection potentiated PKR activation and synergistically induced the expression of IFNβ and IL-10. Importantly, in vivo coinfection of C57BL/6 mice corroborated the in vitro data. The exacerbation effect of RNA virus on parasite infection may be specific because coinfection with dengue virus (DENV2) exerted the opposite effect on parasite load. Conclusions Altogether, our data suggest that coinfections with specific RNA viruses shared by vectors or reservoirs of Leishmania may enhance and sustain the activation of host cellular RNA sensors, resulting in aggravation of the parasite infection. The present work highlights new perspectives for the investigation of antiviral pathways as important modulators of protozoan infections.

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Dynamic of the Cellular Immune Response at the Dermal Site ofLeishmania (L.) amazonensisandLeishmania (V.) braziliensisInfection inSapajus apellaPrimate

Cited by 15 publications

References 25 publications

Therapeutic effect of ursolic acid in experimental visceral leishmaniasis

Therapeutic effect of ursolic acid in experimental visceral leishmaniasis

The Effect of Ursolic Acid on Leishmania (Leishmania) amazonensis Is Related to Programed Cell Death and Presents Therapeutic Potential in Experimental Cutaneous Leishmaniasis

Amazonian Phlebovirus (Bunyaviridae) potentiates the infection of Leishmania (Leishmania) amazonensis: Role of the PKR/IFN1/IL-10 axis

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