CD95 (FAS) and CD178 (FASL) induce the apoptosis of CD4+ and CD8+ cells isolated from the peripheral blood and spleen of dogs naturally infected with Leishmania spp

Silva, Kathlenn Liezbeth Oliveira; Melo, Larissa Martins; Perosso, Juliana; Oliveira, Bruna Brito; Santos, Paulo Sérgio Patto dos; Eugênio, Flávia de Rezende; Lima, Valéria Marçal Felix de

doi:10.1016/j.vetpar.2013.07.012

Cited by 10 publications

(8 citation statements)

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“…In agreement with previously reported results (Lima et al, 2012;Perosso et al, 2014;Silva et al, 2013), we observed an increase in the apoptosis of CD3 + T lymphocytes from the peripheral blood and spleens of dogs with VL. This suggests that apoptosis may be involved in the low lymphoproliferative response during this disease, as previously reported by (Esch et al, 2013), and therefore may contribute to the failure of immunity, the emergence of coinfection and the development of neoplasms that are observed in dogs chronically infected by Leishmania spp.…”

Section: Discussionsupporting

confidence: 93%

“…Inhibition of T lymphocyte apoptosis is not complete because it is still detected, suggesting that other inducers of cell death pathways are still active. In fact, other receptors, including transmembrane Fas/FasL (Silva et al, 2013) and soluble Fas/FasL (Perosso et al, 2014) have been shown to be involved in the apoptosis of T lymphocytes (CD3 + , CD4 + and CD8 + ) in dogs with VL.…”

Section: Discussionmentioning

confidence: 99%

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PD-1 function in apoptosis of T lymphocytes in canine visceral leishmaniasis

et al. 2016

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Dogs infected with Leishmania infantum have a reduced number of T lymphocytes. PD-1 (Programmed cell death 1) a new member of the B7-CD28 family that is expressed by immune cells, and its binding to PD-L1 (CD274) or PD-L2 (CD273) induces the deactivation or apoptosis of T cells. This study aimed to evaluate the expression of PD-1 and its ligands, as well as blocking in the induction of apoptosis in T lymphocytes, TNF-α, IL-4 and nitric oxide production by leucokocytes from PBMC and spleen and the parasite load in dogs with visceral leishmaniasis (VL). Our results showed that the expression of PD1 and its ligands was increased in CD3(+) T cells and CD21(+) B lymphocytes within the peripheral blood and splenic mononuclear cells of dogs with VL. In peripheral blood monocytes, only PD-1 ligands exhibited increased expression; however, in spleen macrophages, increased expression of both PD-1 and its ligands was observed. Levels of apoptosis in peripheral blood and splenic T lymphocytes were higher in dogs with VL compared to healthy dogs. Blocking monoclonal antibodies to PD-1 and its ligands in the culture of mononuclear cells from the peripheral blood and spleen decreased the amount of CD3(+) T lymphocyte apoptosis. The concentration of nitric oxide, TNF-α and IL-4 increased in the culture supernatants of peripheral blood mononuclear cells treated with a blocking monoclonal antibody against PD-1. The TNF-α concentration increased in the culture supernatants of splenic cells following all treatments with antibodies blocking PD-1 and its ligands; however, the amount of IL-4 increased only in the presence of a PD-1 blocking agent. Treatment with a PD-1 blocking monoclonal antibody in the mononuclear peripheral blood of dogs with VL reduced the parasite burden while increased TNF-α. We conclude that in canine visceral leishmaniasis, PD-1 and its ligands are involved in the induction of T lymphocyte apoptosis and in regulating the production of nitric oxide, TNF-α, and IL-4, as well as the parasitic load.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

PD-1 function in apoptosis of T lymphocytes in canine visceral leishmaniasis

et al. 2016

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“…Although several of the apoptosis-inducing mechanisms have been studied in the canine VL, [7,18,19], whether NO plays an important role in apoptosis and may contribute to the immunosuppression observed in canine VL has yet to be studied.…”

Section: Introductionmentioning

confidence: 99%

Cellular apoptosis and nitric oxide production in PBMC and spleen from dogs with visceral leishmaniasis

Martini

Andrade

Almeida

et al. 2018

Comparative Immunology, Microbiology and Infectious Diseases

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Nitric oxide (NO) is involved in the death of the Leishmania parasite and regulation of apoptosis. We quantified the frequency of cells producing NO and its levels in the peripheral blood mononuclear cells (PBMC), leukocytes from spleen in Visceral Leishmaniasis (VL) symptomatic dogs and correlated NO levels with apoptosis and parasite load in the spleen. The percentage of NO+ cells and CD14+/NO+ was higher in PBMC and spleen cells in infected dogs than in controls. The levels of NO+ and CD14+/NO+ cells was higher in PBMC, but lower spleen of dogs infected than compared to control. Late apoptosis rates increased in PBMC and spleen of infected dogs compared to controls, and the NO levels and apoptosis not showed correlation. There was a positive correlation between the percentage of cells producing NO in the spleen and parasite load. The NO participates in the immune response in the canine VL, but it is not apoptosis inducer.

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“…Fas and FasL, important molecules in apoptosis, were downregulated by miR-21 [27,28]. Expression levels of Fas and FasL in CD4+ cells from blood and spleen have already been shown to be lower in infected dogs when compared to healthy dogs [29], and the soluble levels Fas (sFas) from spleen leukocytes were lower in dogs with VL compared to controls [30]. Thus, miRNAs are acting in apoptosis pathway that occurs in CVL.…”

Section: Discussionmentioning

confidence: 99%

Relationship of peripheral blood mononuclear cells miRNA expression and parasitic load in canine visceral leishmaniasis

et al. 2018

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Visceral leishmaniasis (VL) in humans is a chronic and often fatal disease if left untreated. Dogs appear to be the main reservoir host for L. infantum infection, however, in many regions other canids such as jackals, foxes, wolves and other mammals, such as hares or black rats, have been implicated as wild reservoirs. Most dogs cannot form an effective immune response against this infection, and this could be modulated by small non-coding RNAs, called microRNAs, responsible for post-transcriptional control of gene expression. Here, we evaluated the expression of miRNAs in peripheral blood mononuclear cells (PBMC) of symptomatic dogs naturally infected with Leishmania (L.) infantum (n = 10) and compared to those of healthy dogs (n = 5). Microarray analysis revealed that miR-21, miR-424, miR-194 and miR-451 had a 3-fold increase in expression, miR-192, miR-503, and miR-371 had a 2-fold increase in expression, whereas a 2-fold reduction in expression was observed for miR-150 and miR-574. Real-time PCR validated the differential expression of miR-21, miR-150, miR-451, miR-192, miR-194, and miR-371. Parasite load of PBMC was measured by real-time PCR and correlated to the differentially expressed miRNAs, showing a strong positive correlation with expression of miR-194, a regular positive correlation with miR-371 expression, and a moderate negative correlation with miR-150 expression in PBMC. These findings suggest that Leishmania infection interferes with miRNAs expression in PBMC, and their correlation with parasite load may help in the identification of therapeutic targets in Canine Visceral Leishmaniasis (CVL).

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CD95 (FAS) and CD178 (FASL) induce the apoptosis of CD4+ and CD8+ cells isolated from the peripheral blood and spleen of dogs naturally infected with Leishmania spp

Cited by 10 publications

References 37 publications

PD-1 function in apoptosis of T lymphocytes in canine visceral leishmaniasis

PD-1 function in apoptosis of T lymphocytes in canine visceral leishmaniasis

Cellular apoptosis and nitric oxide production in PBMC and spleen from dogs with visceral leishmaniasis

Relationship of peripheral blood mononuclear cells miRNA expression and parasitic load in canine visceral leishmaniasis

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