Effects of soluble extracts from Leishmania infantum promastigotes, Toxoplasma gondii tachyzoites on TGF-β mediated pathways in activated CD4+ T lymphocytes

Clemente, Ann Maria; Severini, Carlo; Castronovo, Giuseppe; Tanturli, Michele; Perissi, Eloisa; Cozzolino, Federico; Torcia, Maria Gabriella

doi:10.1016/j.micinf.2014.08.002

Cited by 5 publications

(4 citation statements)

References 43 publications

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“…TGF-␤ production is associated with T. gondii infection and affects immune responses not only to the parasite but also in a systemic manner (18-20, 33, 34). TGF-␤ induction has been associated with phosphatidylserine (PS) expression on the surface of the parasite and soluble factors (20,(35)(36)(37). In the present study, we observed only very minute increases in the amount of TGF-␤ in the cell cultures but could detect increased levels of LAP expression only on the surface of freshly isolated infected NK cells.…”

Section: Discussioncontrasting

confidence: 41%

Downmodulation of Effector Functions in NK Cells upon Toxoplasma gondii Infection

Sultana

Carow

et al. 2017

Infect Immun

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The obligate intracellular parasite can actively infect any nucleated cell type, including cells from the immune system. The rapid transfer of from infected dendritic cells to effector natural killer (NK) cells may contribute to the parasite's sequestration and shielding from immune recognition shortly after infection. However, subversion of NK cell functions, such as cytotoxicity or production of proinflammatory cytokines, such as gamma interferon (IFN-γ), upon parasite infection might also be beneficial to the parasite. In the present study, we investigated the effects of infection on NK cells., infected NK cells were found to be poor at killing target cells and had reduced levels of IFN-γ production. This could be attributed in part to the inability of infected cells to form conjugates with their target cells. However, even upon NK1.1 cross-linking of NK cells, the infected NK cells also exhibited poor degranulation and IFN-γ production. Similarly, NK cells infected were also poor at killing target cells and producing IFN-γ. Increased levels of transforming growth factor β production, as well as increased levels of expression of SHP-1 in the cytosol of infected NK cells upon infection, were observed in infected NK cells. However, the phosphorylation of STAT4 was not altered in infected NK cells, suggesting that transcriptional regulation mediates the reduced IFN-γ production, which was confirmed by quantitative PCR. These data suggest that infection of NK cells by impairs NK cell recognition of target cells and cytokine release, two mechanisms that independently could enhance survival.

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Section: Discussioncontrasting

confidence: 41%

Downmodulation of Effector Functions in NK Cells upon Toxoplasma gondii Infection

Sultana

Carow

et al. 2017

Infect Immun

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“…It has previously been shown that in vitro stimulation of adult PBMCs with P . falciparum antigen induces regulatory T cells [ 9 , 10 , 12 , 35 ]. To investigate whether the propensity of CD4 T cells to differentiate into T regs in response to parasite antigen is influenced by age and/or prior malaria exposure, we measured induction of T regs following in vitro stimulation with P .…”

Section: Resultsmentioning

confidence: 99%

“…falciparum thrombospondin-related adhesive protein ( Pf TRAP) [ 11 ]. This T reg induction mechanism is shared by related protozoal pathogens Toxoplasma and Leishmania [ 35 ] and may represent an immune evasion strategy. The reduced capacity of parasite antigen to induce T regs in heavily malaria exposed children suggests that the host may be able to circumvent parasite induction of T regs , potentially enabling enhanced control of infection.…”

Section: Discussionmentioning

confidence: 99%

Decline of FoxP3+ Regulatory CD4 T Cells in Peripheral Blood of Children Heavily Exposed to Malaria

et al. 2015

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FoxP3+ regulatory CD4 T cells (Tregs) help to maintain the delicate balance between pathogen-specific immunity and immune-mediated pathology. Prior studies suggest that Tregs are induced by P. falciparum both in vivo and in vitro; however, the factors influencing Treg homeostasis during acute and chronic infections, and their role in malaria immunopathogenesis, remain unclear. We assessed the frequency and phenotype of Tregs in well-characterized cohorts of children residing in a region of high malaria endemicity in Uganda. We found that both the frequency and absolute numbers of FoxP3+ Tregs in peripheral blood declined markedly with increasing prior malaria incidence. Longitudinal measurements confirmed that this decline occurred only among highly malaria-exposed children. The decline of Tregs from peripheral blood was accompanied by reduced in vitro induction of Tregs by parasite antigen and decreased expression of TNFR2 on Tregs among children who had intense prior exposure to malaria. While Treg frequencies were not associated with protection from malaria, there was a trend toward reduced risk of symptomatic malaria once infected with P. falciparum among children with lower Treg frequencies. These data demonstrate that chronic malaria exposure results in altered Treg homeostasis, which may impact the development of antimalarial immunity in naturally exposed populations.

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“…( L .) infantum chagasi activate the soluble form of latent TGF- β complex favoring the persistence of parasites within infected macrophages through induction of TGF- β mediated anti-inflammatory mechanisms [19]. The role of TGF- β as a key predictive factor of enhanced susceptibility to the disease was also demonstrated in BALB/c mice immunized with whole antigens of L .…”

Section: Discussionmentioning

confidence: 99%

Morinda citrifolia Linn. Reduces Parasite Load and Modulates Cytokines and Extracellular Matrix Proteins in C57BL/6 Mice Infected with Leishmania (Leishmania) amazonensis

Almeida-Souza¹,

Cardoso²,

Souza³

et al. 2016

PLoS Negl Trop Dis

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The absence of an effective vaccine and the debilitating chemotherapy for Leishmaniasis demonstrate the need for developing alternative treatments. Several studies conducted with Morinda citrifolia have shown various biological activities, including antileishmanial activity, however its mechanisms of action are unknown. This study aimed to analyze the in vivo activity of M. citrifolia fruit juice (Noni) against Leishmania (Leishmania) amazonensis in C57BL/6 mice. M. citrifolia fruit juice from the Brazilian Amazon has shown the same constitution of other juices produced around the world and liquid chromatography–mass spectrometry analysis identified five compounds: deacetylasperulosidic acid, asperulosidic acid, rutin, nonioside B and nonioside C. Daily intragastric treatment with Noni was carried out after 55 days of L. (L.) amazonensis infection in C57BL/6 mice. Parasitic loads, cytokine and extracellular protein matrix expressions of the lesion site were analyzed by qPCR. Histopathology of the lesion site, lymph nodes and liver were performed to evaluate the inflammatory processes. Cytokines and biochemical parameters of toxicity from sera were also evaluated. The Noni treatment at 500 mg.kg-1.day-1 for 60 days decreased the lesion size and parasitic load in the footpad infected with L. (L.) amazonensis. The site of infection also showed decreased inflammatory infiltrates and decreased cytokine expressions for IL-12, TNF-α, TGF-β and IL-10. On the other hand, Noni treatment enhanced the extracellular matrix protein expressions of collagen IV, fibronectin and laminin in the infected footpad as well collagen I and II, fibronectin and laminin in the mock-infected footpads. No toxicity was observed at the end of treatment. These data show the efficacy of Noni treatment.

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Effects of soluble extracts from Leishmania infantum promastigotes, Toxoplasma gondii tachyzoites on TGF-β mediated pathways in activated CD4+ T lymphocytes

Cited by 5 publications

References 43 publications

Downmodulation of Effector Functions in NK Cells upon Toxoplasma gondii Infection

Downmodulation of Effector Functions in NK Cells upon Toxoplasma gondii Infection

Decline of FoxP3+ Regulatory CD4 T Cells in Peripheral Blood of Children Heavily Exposed to Malaria

Morinda citrifolia Linn. Reduces Parasite Load and Modulates Cytokines and Extracellular Matrix Proteins in C57BL/6 Mice Infected with Leishmania (Leishmania) amazonensis

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