Immune response to Leishmania (Leishmania) chagasi infection is reduced in malnourished BALB/c mice

Serafim, Tiago D.; Malafaia, Guilherme; Silva, Marcelo Eustáquio; Pedrosa, Maria Lúcia; Rezende, Simone Aparecida

doi:10.1590/s0074-02762010000600014

Cited by 27 publications

(28 citation statements)

References 32 publications

(33 reference statements)

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“…Comparative analyses of parasite burden in the liver and spleen demonstrated early and high levels of parasitism detectable at 2 weeks post-infection; these remained fairly constant in those organs up to week 8. Our data differs from that described for Leishmania chagasi (MHOM/BR/1974/M2682 strain) which peaks at four weeks post-infection in the liver of infected mice [18]. We therefore selected week 6 for administration of the different treatment regimens and two weeks afterwards for data collection.…”

Section: Discussionmentioning

confidence: 91%

Association of Liposome-Encapsulated Trivalent Antimonial with Ascorbic Acid: An Effective and Safe Strategy in the Treatment of Experimental Visceral Leishmaniasis

et al. 2014

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Background:Visceral leishmaniasis (VL) is a chronic debilitating disease endemic in tropical and subtropical areas, caused by protozoan parasites of the genus Leishmania. Annually, it is estimated the occurrence of 0.2 to 0.4 million new cases of the disease worldwide. Considering the lack of an effective vaccine the afflicted population must rely on both, an accurate diagnosis and successful treatment to combat the disease. Here we propose to evaluate the efficacy of trivalent antimonial encapsulated in conventional liposomes, in association with ascorbic acid, by monitoring its toxicity and efficacy in BALB/c mice infected with Leishmania infantum.Methodology/Principal Findings:Infected mice were subjected to single-dose treatments consisting in the administration of either free or liposome-encapsulated trivalent antimony (SbIII), in association or not with ascorbic acid. Parasite burden was assessed in the liver, spleen and bone marrow using the serial limiting dilution technique. After treatment, tissue alterations were examined by histopathology of liver, heart and kidney and confirmed by serum levels of classic biomarkers. The phenotypic profile of splenocytes was also investigated by flow cytometry. Treatment with liposome-encapsulated SbIII significantly reduced the parasite burden in the liver, spleen and bone marrow. Co-administration of ascorbic acid, with either free SbIII or its liposomal form, did not interfere with its leishmanicidal activity and promoted reduced toxicity particularly to the kidney and liver tissues.Conclusions/Significance:Among the evaluated posological regimens treatment of L. infantum-infected mice with liposomal SbIII, in association with ascorbic acid, represented the best alternative as judged by its high leishmanicidal activity and absence of detectable toxic effects. Of particular importance, reduction of parasite burden in the bone marrow attested to the ability of SbIII-carrying liposomes to efficiently reach this body compartment.

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Section: Discussionmentioning

confidence: 91%

Association of Liposome-Encapsulated Trivalent Antimonial with Ascorbic Acid: An Effective and Safe Strategy in the Treatment of Experimental Visceral Leishmaniasis

et al. 2014

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“…Nevertheless, we found about a 16-fold reduction in the percent of lymph node barrier function, and conclude that the early parasite dissemination is the result of the impaired capacity of the lymph node to contain the parasite locally. Since the total extradermal parasite burdens (local draining lymph nodes, spleen, and liver) were comparable between the two groups, it appears unlikely that early increase in the parasite visceralization was due to defective local parasite killing in the lymph node (although this is likely to be an issue later in the course of infection in the malnourished host [45]) or a difference in the rate of the parasite multiplication. Furthermore, hematogenous dissemination of L. donovani from the site of skin infection is not likely to contribute significantly to the malnutrition-related parasite visceralization because the parasite burdens in the skin and draining LN were no different in the WN and PND mice at an early time point.…”

Section: Discussionmentioning

confidence: 99%

The Malnutrition-Related Increase in Early Visceralization of Leishmania donovani Is Associated with a Reduced Number of Lymph Node Phagocytes and Altered Conduit System Flow

et al. 2013

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In a murine model of moderate childhood malnutrition we found that polynutrient deficiency led to a 4–5-fold increase in early visceralization of L. donovani (3 days post-infection) following cutaneous infection and a 16-fold decrease in lymph node barrier function (p<0.04 for all). To begin to understand the mechanistic basis for this malnutrition-related parasite dissemination we analyzed the cellularity, architecture, and function of the skin-draining lymph node. There was no difference in the localization of multiple cell populations in the lymph node of polynutrient deficient (PND) mice, but there was reduced cellularity with fewer CD11c+dendritic cells (DCs), fibroblastic reticular cells (FRCs), MOMA-2+ macrophages, and CD169+ subcapsular sinus macrophage (p<0.05 for all) compared to the well-nourished (WN) mice. The parasites were equally co-localized with DCs associated with the lymph node conduit network in the WN and PND mice, and were found in the high endothelial venule into which the conduits drain. When a fluorescent low molecular weight (10 kD) dextran was delivered in the skin, there was greater efflux of the marker from the lymph node conduit system to the spleens of PND mice (p<0.04), indicating that flow through the conduit system was altered. There was no evidence of disruption of the conduit or subcapsular sinus architecture, indicating that the movement of parasites into the subcortical conduit region was due to an active process and not from passive movement through a leaking barrier. These results indicate that the impaired capacity of the lymph node to act as a barrier to dissemination of L. donovani infection is associated with a reduced number of lymph node phagocytes, which most likely leads to reduced capture of parasites as they transit through the sinuses and conduit system.

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“…Linkenhoker and Lindton [28] assessed the effects of the nesting material on the body weights of mice infected with Toxoplasma and observed that the nesting material did not significantly alter the weights of mice after Toxoplasma inoculation, but did decrease the rates of growth prior to inoculation. The body weight decrease may not be exclusively specific to the T. gondii , but also to other parasitic protozoe for example Trypanosoma cruzi [31], Leishmania sp, [32] and Plasmodium sp . [33].…”

Section: Discussionmentioning

confidence: 99%

Toxoplasma gondii Decreases the Reproductive Fitness in Mice

et al. 2014

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Toxoplasma gondii is a common protozoan parasite that infects warm-blooded animals throughout the world, including mice and humans. During infection, both, the parasite and the host, utilize various mechanisms to maximize their own reproductive success. Mice and humans are both the intermediate hosts for Toxoplasma gondii, which forms specialized vacuoles containing reproductive cysts in the formers’ tissue. As half of the human population is infected, developing a disease called toxoplasmosis, along with an ever-growing number of couples suffering with idiopathic infertility, it is therefore surprising that there is a lack of research on how Toxoplasma gondii can alter reproductive parameters. In this study, a detailed histometric screening of the testicular function along with the levels of the pituitary luteinizing hormone (LH) were analysed in infected mice. Data on relative testis and epididymis weight, and sperm count were also collected. Based on the results obtained, the level of LH in the urine of Toxoplasma gondii infected mice was lower compared to the control. In direct correlation with the hormone level, testicular function and sperm production was also significantly lower in Toxoplasma gondii positive group using sperm count and histometric analysis as a marker. Not only were the number of leptotene primary spermatocytes and spermatids lowered, but the number of Sertoli cells and the tubule diameter were elevated. In parallel, a pilot epigenetic study on global testicular methylation, and specific methylation of Crem, Creb1 and Hspa1genes essential for successfully ongoing spermatogenesis was performed. Global methylation was elevated in Toxoplasma infected mice, and differences in the DNA methylation of selected genes were detected between the Toxoplasma positive and control group. These findings demonstrate a direct relation between Toxoplasma gondii infection and the decrease of male reproductive fitness in mice, which may contribute to an increase of idiopathic infertility in humans.

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Immune response to Leishmania (Leishmania) chagasi infection is reduced in malnourished BALB/c mice

Cited by 27 publications

References 32 publications

Association of Liposome-Encapsulated Trivalent Antimonial with Ascorbic Acid: An Effective and Safe Strategy in the Treatment of Experimental Visceral Leishmaniasis

Association of Liposome-Encapsulated Trivalent Antimonial with Ascorbic Acid: An Effective and Safe Strategy in the Treatment of Experimental Visceral Leishmaniasis

The Malnutrition-Related Increase in Early Visceralization of Leishmania donovani Is Associated with a Reduced Number of Lymph Node Phagocytes and Altered Conduit System Flow

Toxoplasma gondii Decreases the Reproductive Fitness in Mice

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