Histopathological studies of visceralized Leishmania (Leishmania) amazonensis in mice experimentally infected

Abreu-Silva, Ana Lúcia; Calabrese, Kátia da Silva; Cupolilo, Sônia Maria Neumann; Cardoso, Flávia de Oliveira; Souza, C. S. F.; Costa, Salvatore

doi:10.1016/j.vetpar.2004.03.002

Cited by 38 publications

(26 citation statements)

References 22 publications

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“…Among them, Leishmania amazonensis presents a particular importance, as it is one of the main species capable of causing human disease with a broad spectrum of clinical manifestations, ranging from cutaneous to visceral leishmaniasis [2], [3]. In one study, it was also observed that BALB/c mice experimentally infected with L. amazonensis developed visceralization of the parasites in different organs, such as the brain, liver, spleen, and bone marrow, characterizing a diagnosis of murine visceral leishmaniasis [4].…”

Section: Introductionmentioning

confidence: 99%

Identification of Differentially Expressed Proteins from Leishmania amazonensis Associated with the Loss of Virulence of the Parasites

et al. 2014

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BackgroundThe present study analyzed whether or not the in vitro cultivation for long periods of time of pre-isolated Leishmania amazonensis from lesions of chronically infected BALB/c mice was able to interfere in the parasites' infectivity using in vivo and in vitro experiments. In addition, the proteins that presented a significant decrease or increase in their protein expression content were identified applying a proteomic approach.Methodology/Principal FindingsParasites were cultured in vitro for 150 days. Aliquots were collected on the day 0 of culture (R0), as well as after ten (R10; 50 days of culture), twenty (R20; 100 days of culture), and thirty (R30; 150 days of culture) passages, and were used to analyze the parasites' in vitro and in vivo infectivity, as well as to perform the proteomic approach. Approximately 837, 967, 935, and 872 spots were found in 2-DE gels prepared from R0, R10, R20, and R30 samples, respectively. A total of 37 spots presented a significant decrease in their intensity of expression, whereas a significant increase in protein content during cultivation could be observed for 19 proteins (both cases >2.0 folds). Some of these identified proteins can be described, such as diagnosis and/or vaccine candidates, while others are involved in the infectivity of Leishmania. It is interesting to note that six proteins, considered hypothetical in Leishmania, showed a significant decrease in their expression and were also identified.Conclusions/SignificanceThe present study contributes to the understanding that the cultivation of parasites over long periods of time may well be related to the possible loss of infectivity of L. amazonensis. The identified proteins that presented a significant decrease in their expression during cultivation, including the hypothetical, may also be related to this loss of parasites' infectivity, and applied in future studies, including vaccine candidates and/or immunotherapeutic targets against leishmaniasis.

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Section: Introductionmentioning

confidence: 99%

Identification of Differentially Expressed Proteins from Leishmania amazonensis Associated with the Loss of Virulence of the Parasites

et al. 2014

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“…distant from the inoculation site is considered a common finding in hamsters and mice that are experimentally infected with inocula that contain a high parasite concentration (13,15,17,39,40). This also correlated with lesion size and consequently with infection severity (15).…”

Section: Discussionmentioning

confidence: 94%

Comparative Evaluation of Lesion Development, Tissue Damage, and Cytokine Expression in Golden Hamsters (Mesocricetus auratus) Infected by Inocula with Different Leishmania (Viannia) braziliensis Concentrations

et al. 2014

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The golden hamster (Mesocricetus auratus) is a susceptible model to Leishmania (Viannia) spp.; however, available studies employ different infection protocols, which account for clinical and pathological presentation differences. Herein, L. (V.) braziliensis preparations were standardized to contain 10 4 , 10 5 , or 10 6 parasites to determine an optimal inoculum that ensured cutaneous lesions without causing a disseminated infection in hamsters. Lesion development was followed for 105 days by size measurements, and skin, draining lymph node, spleen, and sera were investigated to check parasite load, spleen visceralization, cytokine expression, histopathological changes, and anti-Leishmania IgG levels. The lesion emergence time was inversely proportional to the parasite concentration in the inocula. Animals infected by 10 4 parasites presented nodular lesions, while those infected with 10 6 parasites often exhibited ulcerated lesions. The differences in the final lesion sizes were observed between 10 4 and 10 5 inocula or 10 4 and 10 6 inocula. High IFNG expression, anti-Leishmania IgG levels, and parasite load occurred independently of the inoculum used. A mild inflammatory skin involvement was observed in animals infected with 10 4 parasites, while extensive tissue damage and parasite spleen visceralization occurred with 10 5 and 10 6 parasites. These results indicate that inocula with different concentrations of parasites generate differences in the time of lesion emergence, clinical presentation, and systemic commitment, despite high and similar IFNG expression and parasite load. This suggests that a modulation in the immune response to different parasite numbers occurs in an early phase of the infection, which could dictate the establishment and magnitude of the chronic phase of the disease.

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“…The immune response to L. amazonensis varies in accordance with the genetic background of the host. L. amazonensis causes severe lesions at cutaneous inoculation sites in the highly susceptible CBA and BALB/c mouse strains [4,10,11], while this same parasite causes chronic non-healing lesions in L. major -resistant strains, such as C57BL/6, C3H and C57BL/10 [10,12-14]. In response to infection by L. amazonensis , highly susceptible BALB/c mice mount a Th2-type of immune response, while C57BL/6 mice develop a non-Th1-type of immune response [15].…”

Section: Introductionmentioning

confidence: 99%

A comparison of two distinct murine macrophage gene expression profiles in response to Leishmania amazonensisinfection

et al. 2012

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BackgroundThe experimental murine model of leishmaniasis has been widely used to characterize the immune response against Leishmania. CBA mice develop severe lesions, while C57BL/6 present small chronic lesions under L. amazonensis infection. Employing a transcriptomic approach combined with biological network analysis, the gene expression profiles of C57BL/6 and CBA macrophages, before and after L. amazonensis infection in vitro, were compared. These strains were selected due to their different degrees of susceptibility to this parasite.ResultsThe genes expressed by C57BL/6 and CBA macrophages, before and after infection, differ greatly, both with respect to absolute number as well as cell function. Uninfected C57BL/6 macrophages express genes involved in the deactivation pathway of macrophages at lower levels, while genes related to the activation of the host immune inflammatory response, including apoptosis and phagocytosis, have elevated expression levels. Several genes that participate in the apoptosis process were also observed to be up-regulated in C57BL/6 macrophages infected with L. amazonensis, which is very likely related to the capacity of these cells to control parasite infection. By contrast, genes involved in lipid metabolism were found to be up-regulated in CBA macrophages in response to infection, which supports the notion that L. amazonensis probably modulates parasitophorous vacuoles in order to survive and multiply in host cells.ConclusionThe transcriptomic profiles of C57BL/6 macrophages, before and after infection, were shown to be involved in the macrophage pathway of activation, which may aid in the control of L. amazonensis infection, in contrast to the profiles of CBA cells.

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Histopathological studies of visceralized Leishmania (Leishmania) amazonensis in mice experimentally infected

Cited by 38 publications

References 22 publications

Identification of Differentially Expressed Proteins from Leishmania amazonensis Associated with the Loss of Virulence of the Parasites

Identification of Differentially Expressed Proteins from Leishmania amazonensis Associated with the Loss of Virulence of the Parasites

Comparative Evaluation of Lesion Development, Tissue Damage, and Cytokine Expression in Golden Hamsters (Mesocricetus auratus) Infected by Inocula with Different Leishmania (Viannia) braziliensis Concentrations

A comparison of two distinct murine macrophage gene expression profiles in response to Leishmania amazonensisinfection

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