Influence of the inoculation route in BALB/c mice infected by Leishmania infantum

Rolão, Nuno; Melo, Cláudia Moura de; Campino, Lenea

doi:10.1016/j.actatropica.2003.09.010

Cited by 36 publications

(33 citation statements)

References 14 publications

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“…route was chosen because it has been proven to result in a higher homogeneity among infections than the i.v. one (54). In this model, LiSIR2 ϩ/Ϫ parasites, which were unable to cause disease in susceptible BALB/c mice, did induce protection against infection with virulent L. infantum challenge.…”

Section: Discussionmentioning

confidence: 92%

SIR2-Deficient Leishmania infantum Induces a Defined IFN-γ/IL-10 Pattern That Correlates with Protection

Silvestre

Cordeiro-da-Silva

Santarém

et al. 2007

The Journal of Immunology

100

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The ability to manipulate the Leishmania genome to create genetically modified parasites by introducing or eliminating genes is considered a powerful alternative for developing a new generation vaccine against leishmaniasis. Previously, we showed that the deletion of one allele of the Leishmania infantum silent information regulatory 2 (LiSIR2) locus was sufficient to dramatically affect amastigote axenic proliferation. Furthermore, LiSIR2 single knockout (LiSIR2+/−) amastigotes were unable to replicate in vitro inside macrophages. Because this L. infantum mutant persisted in BALB/c mice for up to 6 wk but failed to establish an infection, we tested its ability to provide protection toward a virulent L. infantum challenge. Strikingly, vaccination with a single i.p. injection of LiSIR2+/− single knockout elicits complete protection. Thus, vaccinated BALB/c mice showed a reversal of T cell anergy with specific anti-Leishmania cytotoxic activity and high levels of NO production. Moreover, vaccinated mice simultaneously generated specific anti-Leishmania IgG Ab subclasses suggestive of both type 1 and type 2 responses. A strong correlation was found between the elimination of the parasites and an increased Leishmania-specific IFN-γ/IL-10 ratio. Therefore, we propose that the polarization to a high IFN-γ/low IL-10 ratio after challenge is a clear indicator of vaccine success. Furthermore these mutants, which presented attenuated virulence, represent a good model to understand the correlatives of protection in visceral leishmaniasis.

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Section: Discussionmentioning

confidence: 92%

SIR2-Deficient Leishmania infantum Induces a Defined IFN-γ/IL-10 Pattern That Correlates with Protection

Silvestre

Cordeiro-da-Silva

Santarém

et al. 2007

The Journal of Immunology

100

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“…To determine the course of infection of our model, 20 female BALB/c mice, 6 to 8 weeks old, were infected intraperitoneally with 1.0 ϫ 10 8 stationary-phase L. infantum promastigotes (21)(22)(23)(24). At days 7, 14, 21, and 30, five animals were euthanatized in a CO 2 chamber for parasite load determinations, as detailed below.…”

Section: Methodsmentioning

confidence: 99%

Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis

Cunha-Júnior

Martins

Canto‐Cavalheiro

et al. 2016

Antimicrob Agents Chemother

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e Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is the second major cause of death by parasites, after malaria. The arsenal of drugs against leishmaniasis is small, and each has a disadvantage in terms of toxicity, efficacy, price, or treatment regimen. Our group has focused on studying new drug candidates as alternatives to current treatments. The pterocarpanquinone LQB-118 was designed and synthesized based on molecular hybridization, and it exhibited antiprotozoal and antileukemic cell line activities. Our previous work demonstrated that LQB-118 was an effective treatment for experimental cutaneous leishmaniasis. In this study, we observed that treatment with 10 mg/kg of body weight/day LQB-118 orally inhibited the development of hepatosplenomegaly with a 99% reduction in parasite load. An in vivo toxicological analysis showed no change in the clinical, biochemical, or hematological parameters. Histologically, all of the analyzed organs were normal, with the exception of the liver, where focal points of necrosis with leukocytic infiltration were observed at treatment doses 5 times higher than the therapeutic dose; however, these changes were not accompanied by an increase in transaminases. Our findings indicate that LQB-118 is effective at treating different clinical forms of leishmaniasis and presents no relevant signs of toxicity at therapeutic doses; thus, this framework is demonstrated suitable for developing promising drug candidates for the oral treatment of leishmaniasis.

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“…The course of visceral infection by L. chagasi in a Balb/c mouse strictly mimics the infection by L. donovani, since the mouse initially expresses a susceptible phenotype, but subsequently develops its self-cure (7). Most studies employing strains of visceral leishmaniasis have been performed with 10 7 parasites per mouse, although variability among injection doses has limited the comparison of results (8). Infection by L. donovani in mice results in early increase of parasite burden and its subsequent control during the infection course (7).…”

Section: Chagasi Both Agents Of Visceral Leishmaniasis In Humans (5)mentioning

confidence: 99%

Experimental infection with Leishmania chagasi in immunosuppressed Balb/c mice: cytokines and parasite burdens

Hoffmann¹,

Machado²,

Gaio³

et al. 2009

J. Venom. Anim. Toxins incl. Trop. Dis

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ABSTRACT:The immune response in leishmaniasis may result in a polarization of the T lymphocyte subpopulation, altering cell phenotype and resulting in immune protection or disease exacerbation. Leishmania may persist in the body either during asymptomatic infections or after treatment, which represents high risk under immunosuppression. The objective of this study was to evaluate the effect of infection with immunosuppression by dexamethasone associated with pentoxifylline on animal weight, spleen weight, spleen and hepatic parasitic load and immunopathology, as well as the IFN-γ and IL-10 production in spleen cell culture of Balb/c mice infected with Leishmania chagasi. The infection did not cause body weight gain in animals, but both the weight and size of the spleen were increased. The immunosuppression using dexamethasone associated with pentoxifylline affected body weight gain and spleen weight and size in both infected and non-infected animals. The immunosuppression did not significantly alter the course of the splenic or hepatic parasite burden. Dexamethasone and pentoxifylline significantly affected cytokine production, but did not influence the Th1/Th2 ratio in infected animals.

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Influence of the inoculation route in BALB/c mice infected by Leishmania infantum

Cited by 36 publications

References 14 publications

SIR2-Deficient Leishmania infantum Induces a Defined IFN-γ/IL-10 Pattern That Correlates with Protection

SIR2-Deficient Leishmania infantum Induces a Defined IFN-γ/IL-10 Pattern That Correlates with Protection

Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis

Experimental infection with Leishmania chagasi in immunosuppressed Balb/c mice: cytokines and parasite burdens

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