Infection pattern and immune response in the spleen and liver of BALB/c mice intracardially infected with Leishmania donovani amastigotes

Mukherjee, Pritish; Ghosh, Asish Kumar; Ghose, A.M.

doi:10.1016/s0165-2478(03)00021-x

Cited by 32 publications

(44 citation statements)

References 32 publications

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“…In infected dogs, asymptomatic or not, the level of liver TNF-a was higher compared to the spleen from the same animals. These results are similar to those obtained with BALB/c mice infected with L. (L.) donovani, in which the level of liver TNF-a was higher than that observed in the spleen (Mukherjee et al, 2003). In this study, observation verified that the level of TNF-a was higher in the liver of the symptomatic dogs than in the asymptomatic.…”

Section: Discussionsupporting

confidence: 90%

“…These results suggest that the immune response to control the spread of the parasite in both organs is regulated by similar mechanisms, possibly without IL-4 participation. Similar results were observed in mice experimentally infected with L. (L.) donovani (Mukherjee et al, 2003) or with L. (L.) infantum (Rolão et al, 2007).…”

Section: Discussionsupporting

confidence: 85%

“…Studies conducted on BALB/c mice infected with L. (L.) donovani (Mukherjee et al, 2003;Rolão et al, 2007) showed that the levels of this cytokine in the liver were higher than those verified in the spleen during the course of infection. The production of IL-10 and TGF-b was also observed in the liver and spleen of asymptomatic and symptomatic dogs infected with L. (L.) chagasi Lage et al, 2007), In addition, the level of IL-10 in the liver of asymptomatic dogs showed a positive linear correlation with the level of parasite load in this organ.…”

Section: Discussionmentioning

confidence: 90%

“…This result is different than that from other reports. In studies conducted on BALB/c mice infected with L. (L.) donovani (Mukherjee et al, 2003;Rolão et al, 2007), the level of IL-4 in the spleen was higher than that in the liver, during the course of infection. The difference between the two studies can be explained by the animal model used in each study and by the fact that the dogs in this study were naturally infected and therefore no information was available regarding when infection started or what moment the examination represented during the course of the disease.…”

Section: Discussionmentioning

confidence: 94%

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Evaluation of TNF-α, IL-4, and IL-10 and parasite density in spleen and liver ofL. (L.) chagasinaturally infected dogs

Michelin

Perri

Lima

2011

Annals of Tropical Medicine & Parasitology

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Dogs are the main domestic reservoirs of L. (L.) chagasi. Once in the vertebrate host, the parasite can cause visceral leishmaniasis, which can also be transmitted to humans. Cytokines are key elements of the host immune response against Leishmania spp. To investigate whether tumor necrosis factor (TNF)-a, interleukin (IL)-4 and IL-10 are associated with pattern infection in dogs, these cytokines were quantified in the spleen and liver of dogs naturally infected with L. (L.) chagasi, with or without clinical manifestations, and their levels were correlated with the parasite load verified in these organs. A total of 40 adult dogs naturally infected with L. (L.) chagasi were assessed, together with 12 uninfected control dogs. Samples from spleen and liver were used to determine the cytokine levels by capture ELISA and for quantifying parasite load by real-time PCR. Statistical analysis was performed using the minimum Chi square method and group means were compared using the Tukey test. TNF-a, IL-4 and IL-10 levels in infected dogs were higher than in control groups; the liver was the main cytokine-producing organ during infection. The level of splenic TNF-a showed correlation with parasite load and may represent an important marker for infection process evolution, with the participation of IL-10. These results may contribute to a clearer understanding of the immune response in dogs infected with L. (L.) chagasi, which may lead to the development of prophylactic or preventive measures for these animals.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 94%

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Evaluation of TNF-α, IL-4, and IL-10 and parasite density in spleen and liver ofL. (L.) chagasinaturally infected dogs

Michelin

Perri

Lima

2011

Annals of Tropical Medicine & Parasitology

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“…Thus, we decided to test its protective capacity and dissect the mechanism leading to the resistance to reinfection in the BALB/c mice model. Although BALB/c mice are susceptible to visceral leishmaniasis, the development of the infection is self-controlled (53). These mice are considered a better model for subclinical infection than for progressive disease (6).…”

Section: Discussionmentioning

confidence: 99%

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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Evaluation of parasitological and immunological parameters of Leishmania chagasi infection in BALB/c mice using different doses and routes of inoculation of parasites

et al. 2011

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Experimental vaccines to protect against visceral leishmaniasis (VL) have been developed by using BALB/c mice infected with a large (10⁷ to 10⁸) inoculum of parasites. Remarkably, prior literature has reported that the poor protection observed is mainly due to the high susceptibility of this strain. To determine factors inherent to mice that might abrogate vaccine-induced efficacy, the present research sought to investigate the impact of the administration of different infective inoculums of Leishmania chagasi (syn. L. infantum) in BALB/c mice, evaluating subcutaneous and intravenous routes of administration as well as parasitological and immunological parameters over different periods of time. This study shows that the injection of a highly infective inoculum in mice, through both subcutaneous and intravenous routes, results in a sustained infection. The mice developed a high parasite load in the liver; however, these values diminished over time. This result did not corroborate with the parasite load in the bone marrow and brain and proved to be expressively different in the spleen and draining lymph nodes, where the values increased over time. Mice infected with a low dose of parasites (10³) showed a certain resistance against infection, based mainly on the IFN-γ and oxide nitric production. Considering all the elements, it could be concluded that the models employing high doses (10⁷) of L. chagasi in BALB/c mice can bring about an imbalance in the animals' immune response, thus allowing for the development of the disease at the expense of efficacy within the vaccine candidates.

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Infection pattern and immune response in the spleen and liver of BALB/c mice intracardially infected with Leishmania donovani amastigotes

Cited by 32 publications

References 32 publications

Evaluation of TNF-α, IL-4, and IL-10 and parasite density in spleen and liver ofL. (L.) chagasinaturally infected dogs

Evaluation of TNF-α, IL-4, and IL-10 and parasite density in spleen and liver ofL. (L.) chagasinaturally infected dogs

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

Evaluation of parasitological and immunological parameters of Leishmania chagasi infection in BALB/c mice using different doses and routes of inoculation of parasites

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