Dataset Information

Vaccination with L. infantum chagasi nucleosomal histones confers protection against new world cutaneous leishmaniasis caused by Leishmania braziliensis.

ABSTRACT:

Background

Nucleosomal histones are intracellular proteins that are highly conserved among Leishmania species. After parasite destruction or spontaneous lysis, exposure to these proteins elicits a strong host immune response. In the present study, we analyzed the protective capability of Leishmania infantum chagasi nucleosomal histones against L. braziliensis infection using different immunization strategies.

Methodology/principal findings

BALB/c mice were immunized with either a plasmid DNA cocktail (DNA) containing four Leishmania nucleosomal histones or with the DNA cocktail followed by the corresponding recombinant proteins plus CpG (DNA/Protein). Mice were later challenged with L. braziliensis, in the presence of sand fly saliva. Lesion development, parasite load and the cellular immune response were analyzed five weeks after challenge. Immunization with either DNA alone or with DNA/Protein was able to inhibit lesion development. This finding was highlighted by the absence of infected macrophages in tissue sections. Further, parasite load at the infection site and in the draining lymph nodes was also significantly lower in vaccinated animals. This outcome was associated with increased expression of IFN-? and down regulation of IL-4 at the infection site.

Conclusion

The data presented here demonstrate the potential use of L. infantum chagasi nucleosomal histones as targets for the development of vaccines against infection with L. braziliensis, as shown by the significant inhibition of disease development following a live challenge.

SUBMITTER: Carneiro MW

PROVIDER: S-EPMC3527524 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Vaccination with L. infantum chagasi nucleosomal histones confers protection against new world cutaneous leishmaniasis caused by Leishmania braziliensis.

Carneiro Marcia W MW Santos Diego M DM Fukutani Kiyoshi F KF Clarencio Jorge J Miranda Jose Carlos JC Brodskyn Claudia C Barral Aldina A Barral-Netto Manoel M Soto Manuel M de Oliveira Camila I CI

PloS one 20121220 12

<h4>Background</h4>Nucleosomal histones are intracellular proteins that are highly conserved among Leishmania species. After parasite destruction or spontaneous lysis, exposure to these proteins elicits a strong host immune response. In the present study, we analyzed the protective capability of Leishmania infantum chagasi nucleosomal histones against L. braziliensis infection using different immunization strategies.<h4>Methodology/principal findings</h4>BALB/c mice were immunized with either a ...[more]

PMID: 23284976

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Project description:BackgroundA recombinant cysteine proteinase from Leishmania (Leishmania) infantum chagasi (rLdccys1) was previously shown to induce protective immune responses against murine and canine visceral leishmaniasis. These findings encouraged us to use rLdccys1 in the immunotherapy of naturally infected dogs from Teresina, Piauí, a region of high incidence of visceral leishmaniasis in Brazil.Methodology/principal findingsThirty naturally infected mongrel dogs displaying clinical signs of visceral leishmaniasis were randomly divided in three groups: one group received three doses of rLdccys1 in combination with the adjuvant Propionibacterium acnes at one month interval between each dose; a second group received three doses of P. acnes alone; a third group received saline. The main findings were: 1) dogs that received rLdccys1 with P. acnes did not display increase of the following clinical signs: weight loss, alopecia, onychogryphosis, cachexia, anorexia, apathy, skin lesions, hyperkeratosis, ocular secretion, and enlarged lymph nodes; they also exhibited a significant reduction in the spleen parasite load in comparison to the control dogs; 2) rLdccys1-treated dogs exhibited a significant delayed type cutaneous hypersensitivity elicited by the recombinant antigen, as well as high IgG2 serum titers and low IgG1 serum titers; sera from rLdccys1-treated dogs also contained high IFN-? and low IL-10 concentrations; 3) control dogs exhibited all of the clinical signs of visceral leishmaniasis and had low serum IgG2 and IFN-? levels and high concentrations of IgG1 and IL-10; 4) all of the dogs treated with rLdccys1 were alive 12 months after treatment, whereas dogs which received either saline or P. acnes alone died within 3 to 7 months.Conclusions/significanceThese findings illustrate the potential use of rLdccys1 as an additional tool for the immunotherapy of canine visceral leishmaniasis and support further studies designed to improve the efficacy of this recombinant antigen for the treatment of this neglected disease.

Dataset Information

Vaccination with L. infantum chagasi nucleosomal histones confers protection against new world cutaneous leishmaniasis caused by Leishmania braziliensis.

Background

Methodology/principal findings

Conclusion

Publications

Vaccination with L. infantum chagasi nucleosomal histones confers protection against new world cutaneous leishmaniasis caused by Leishmania braziliensis.

Similar Datasets

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