Immunopathological Studies of<i>Leishmania amazonensis</i>Infection in Resistant and in Susceptible Mice

Cardoso, Flávia de Oliveira; Souza, Celeste da Silva Freitas de; Mendes, Verônica Gonçalves; Abreu-Silva, Ana Lúcia; Costa, Salvatore; Calabrese, Kátia da Silva

doi:10.1086/652870

Cited by 44 publications

(47 citation statements)

References 44 publications

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“…For the assessment of long-term immunity, mice received the same immunization protocol but were challenged 1 month after the last vaccine dose. In these animals, cross-protection was evaluated by monitoring the sizes of footpad lesions and by determination of the parasite load in lesions after euthanasia by a limiting dilution assay as modified from de Oliveira Cardoso et al (36). …”

Section: Methodsmentioning

confidence: 99%

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Cross-Protective Immunity to Leishmania amazonensis is Mediated by CD4+ and CD8+ Epitopes of Leishmania donovani Nucleoside Hydrolase Terminal Domains

et al. 2014

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The nucleoside hydrolase (NH) of Leishmania donovani (NH36) is a phylogenetic marker of high homology among Leishmania parasites. In mice and dog vaccination, NH36 induces a CD4+ T cell-driven protective response against Leishmania chagasi infection directed against its C-terminal domain (F3). The C-terminal and N-terminal domain vaccines also decreased the footpad lesion caused by Leishmania amazonensis. We studied the basis of the crossed immune response using recombinant generated peptides covering the whole NH36 sequence and saponin for mice prophylaxis against L. amazonensis. The F1 (amino acids 1–103) and F3 peptide (amino acids 199–314) vaccines enhanced the IgG and IgG2a anti-NH36 antibodies to similar levels. The F3 vaccine induced the strongest DTH response, the highest proportions of NH36-specific CD4+ and CD8+ T cells after challenge and the highest expression of IFN-γ and TNF-α. The F1 vaccine, on the other hand, induced a weaker but significant DTH response and a mild enhancement of IFN-γ and TNF-α levels. The in vivo depletion with anti-CD4 or CD8 monoclonal antibodies disclosed that cross-protection against L. amazonensis infection was mediated by a CD4+ T cell response directed against the C-terminal domain (75% of reduction of the size of footpad lesion) followed by a CD8+ T cell response against the N-terminal domain of NH36 (57% of reduction of footpad lesions). Both vaccines were capable of inducing long-term cross-immunity. The amino acid sequence of NH36 showed 93% identity to the sequence of the NH A34480 of L. amazonensis, which also showed the presence of completely conserved predicted epitopes for CD4+ and CD8+ T cells in F1 domain, and of CD4+ epitopes differing by a single amino acid, in F1 and F3 domains. The identification of the C-terminal and N-terminal domains as the targets of the immune response to NH36 in the model of L. amazonensis infection represents a basis for the rationale development of a bivalent vaccine against leishmaniasis.

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Section: Methodsmentioning

confidence: 99%

“…The efficacy of depletion treatment was monitored by the increase of the size of footpad lesions along the 6 weeks of experiment. In addition, the parasite load in lesions on week 6 was evaluated by a limiting dilution assay (36). …”

Section: Methodsmentioning

confidence: 99%

Cross-Protective Immunity to Leishmania amazonensis is Mediated by CD4+ and CD8+ Epitopes of Leishmania donovani Nucleoside Hydrolase Terminal Domains

et al. 2014

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“…amazonensis infection is not limited to the skin. The parasite tends to disseminate to the lymph nodes and can even reach the spleen and liver [23]. The cytokines measured in sera revealed an enhancement of IL-4 and IL-10 caused by L .…”

Section: Discussionmentioning

confidence: 99%

Morinda citrifolia Linn. Reduces Parasite Load and Modulates Cytokines and Extracellular Matrix Proteins in C57BL/6 Mice Infected with Leishmania (Leishmania) amazonensis

Almeida-Souza¹,

Cardoso²,

Souza³

et al. 2016

PLoS Negl Trop Dis

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The absence of an effective vaccine and the debilitating chemotherapy for Leishmaniasis demonstrate the need for developing alternative treatments. Several studies conducted with Morinda citrifolia have shown various biological activities, including antileishmanial activity, however its mechanisms of action are unknown. This study aimed to analyze the in vivo activity of M. citrifolia fruit juice (Noni) against Leishmania (Leishmania) amazonensis in C57BL/6 mice. M. citrifolia fruit juice from the Brazilian Amazon has shown the same constitution of other juices produced around the world and liquid chromatography–mass spectrometry analysis identified five compounds: deacetylasperulosidic acid, asperulosidic acid, rutin, nonioside B and nonioside C. Daily intragastric treatment with Noni was carried out after 55 days of L. (L.) amazonensis infection in C57BL/6 mice. Parasitic loads, cytokine and extracellular protein matrix expressions of the lesion site were analyzed by qPCR. Histopathology of the lesion site, lymph nodes and liver were performed to evaluate the inflammatory processes. Cytokines and biochemical parameters of toxicity from sera were also evaluated. The Noni treatment at 500 mg.kg-1.day-1 for 60 days decreased the lesion size and parasitic load in the footpad infected with L. (L.) amazonensis. The site of infection also showed decreased inflammatory infiltrates and decreased cytokine expressions for IL-12, TNF-α, TGF-β and IL-10. On the other hand, Noni treatment enhanced the extracellular matrix protein expressions of collagen IV, fibronectin and laminin in the infected footpad as well collagen I and II, fibronectin and laminin in the mock-infected footpads. No toxicity was observed at the end of treatment. These data show the efficacy of Noni treatment.

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“…protozoa. In vitro, eosinophils are chemoattracted toward L. amazonensis promastigotes, and in vivo studies have demonstrated eosinophil recruitment to the infection site of L. amazonenesis and L. major [50, 51]. During the initial hours of L. mexicana infection, eosinophils have been observed close to degranulating mast cells at the site of parasite inoculation, suggesting a role in parasite clearance [52].…”

Section: Eosinophilsmentioning

confidence: 99%

“…A contribution of eosinophils during leishmaniasis has recently been examined in more detail by de Oliveira et al [50]. This group showed that infection with L. amazonensis causes an eosinophil-rich infiltrate in primary lesions and draining lymph nodes.…”

Section: Eosinophilsmentioning

confidence: 99%

Eosinophils and mast cells in leishmaniasis

Rodríguez

Wilson

2014

Immunol Res

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Leishmania spp. are parasitic protozoa endemic in tropical and subtropical regions and the causative agent of leishmaniasis, a collection of syndromes whose clinical manifestations vary according to host and pathogen factors. Leishmania spp. are inoculated into the mammalian host by the bite of an infected sand fly, whereupon they are taken up by phagocytosis, convert into the replicative amastigote stage within macrophages, reproduce, spread to new macrophages and cause disease manifestations. A curative response against leishmaniasis depends in the classical activation of macrophages and the IL-12-dependent onset of an adaptive type 1 response characterized by the production of IFN-γ. Emerging evidence suggests that neutrophils, dendritic cells and other immune cells can serve as either temporary or stable hosts for Leishmania spp. Furthermore, it is becoming apparent that the initial interactions of the parasite with resident or early recruited immune cells can shape both the macrophage response and the type of adaptive immune response being induced. In this review, we compile a growing number of studies demonstrating how the earliest interactions of Leishmania spp. with eosinophils and mast cells influence the macrophage response to infection and the development of the adaptive immune response, hence, determining the ultimate outcome of infection.

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Immunopathological Studies ofLeishmania amazonensisInfection in Resistant and in Susceptible Mice

Cited by 44 publications

References 44 publications

Cross-Protective Immunity to Leishmania amazonensis is Mediated by CD4+ and CD8+ Epitopes of Leishmania donovani Nucleoside Hydrolase Terminal Domains

Cross-Protective Immunity to Leishmania amazonensis is Mediated by CD4+ and CD8+ Epitopes of Leishmania donovani Nucleoside Hydrolase Terminal Domains

Morinda citrifolia Linn. Reduces Parasite Load and Modulates Cytokines and Extracellular Matrix Proteins in C57BL/6 Mice Infected with Leishmania (Leishmania) amazonensis

Eosinophils and mast cells in leishmaniasis

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