A cysteine protease from Taenia solium metacestodes induce apoptosis in human CD4+ T-cells

Tato, Patricia; Fernández, Ana; Solano, Sandra; Borgonio, Veronica M.; Garrido, Esperanza; Sepúlveda, Jorge; Molinari, José Luis

doi:10.1007/s00436-003-1008-1

Cited by 41 publications

(25 citation statements)

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“…The depletion of T cells, particularly the CD4 + population Molinari et al 1987), and the suppression of T-cell proliferative responses (Molinari et al 1993a), have been described in cysticercotic pigs. The present results suggest that implanted metacestodes release the suppressive MF in vivo, which may be responsible, along with other molecules such as paramyosin (Laclette et al 1992) and cysteine proteases (White et al 1992;Molinari et al 2000;Tato et al 2004), for suppressing the host immune system. As far as we are aware, the down-modulation induced by F1 is not caused by the stimulation of a particular subset of cells (Th1 or Th2 for instance), but is due to the interaction of this molecule with different cells inducing the inhibition of cytokine production in a non-specific manner.…”

Section: Discussionmentioning

confidence: 84%

The implantation of Taenia solium metacestodes in mice induces down-modulation of T-cell proliferation and cytokine production

et al. 2005

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The purpose of this study was to determine the effect of the implantation of Taenia solium metacestodes and the treatment with suppressive metacestode factor (F1) on the ability of spleen cells from Balb/c mice to produce cytokines. Cytokine production was estimated 12 days following the implantation or 4 days after the last dose of F1 (five doses) by RT-PCR and flow cytometry analyses. Spleen cells were obtained from metacestode-implanted, F1-treated and control mice. They were stimulated with concanavalin A (ConA) ex vivo and used for RT-PCR studies and for CD25 expression and intracellular cytokine production estimations using specific monoclonal antibodies labeled with phycoerithrin or fluorescein. Results of the RT-PCR showed that all cells expressed IFN-gamma, IL-2 and IL-4 mRNAs. IL-10 mRNA was not expressed in any case. Flow cytometry analyses showed that both spleen CD4+ and CD8+ cells from metacestode-implanted or treated-F1 mice expressed significantly diminished percentages of CD25 when compared with control cells (P<0.05). The estimation of intracellular cytokines showed that the production of IL-2 and IL-4 in CD8+ cells, and of IFN-gamma in CD4+ cells from mice implanted with metacestodes was significantly impaired when compared with the values from control cells (P<0.05).

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Section: Discussionmentioning

confidence: 84%

The implantation of Taenia solium metacestodes in mice induces down-modulation of T-cell proliferation and cytokine production

et al. 2005

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“…This hypothesis was discarded because no increased peripheral IL10 levels were detected, neither in supernatant of speciWcally stimulated cells nor in plasma from inXammatory and non-inXammatory NC patients (data not shown). Taking into account the possible existence of suppressive parasite excretion/secretion factors [37][38][39], their presence in sera and CSF was evaluated. As shown in this study, no evidences of suppressive factors were found.…”

Section: Discussionmentioning

confidence: 99%

Neurocysticercosis: local and systemic immune-inflammatory features related to severity

Sáenz¹,

Fleury²,

Chavarría³

et al. 2011

Med Microbiol Immunol

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Neurocysticercosis (NC) is caused by the establishment of Taenia solium cysticerci in the central nervous system. Previous studies have established that neuroinflammation plays a key role in the severity of the disease. However, the relationship between peripheral and local immune response remains inconclusive. This work studies the peripheral and local immune-inflammatory features and their relationships, toward the identification of potential peripheral immunologic features related to severity. A panel of cytokines was measured in paired cerebrospinal fluid (CSF) and in the supernatant of antigen-specific stimulated peripheral blood mononuclear cells samples (SN) in a total of 31 untreated inflammatory and non-inflammatory NC patients. Increased clinical and radiologic severity was associated with an increased cerebrospinal fluid cell count. A peripheral proliferative depression that negatively correlates with CSF cellularity and TNFα and that positively correlates with SN IL5 was observed in severe NC patients. These results provide evidences to support the systemic proliferative response as a biomarker to monitor the level of neuroinflammation, of possible value in the patients' follow-up during treatment.

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“…*p<0.05, **p<0.02 sylation of cysteine-containing proteins (e.g., cysteine proteases) appears to be a common and widespread mechanism, thus parasitic cysteine proteases can be NO targets (Rivero 2006). Recently, it has been demonstrated that T. crassiceps and T. solium metacestodes release cysteine proteases at the host-parasite interface that appear to play a role in favoring parasite survival by breaking IgG and by inducing apoptosis of CD4 + cells (Tato et al 2004;Baig et al 2005). NO may therefore be an important inhibitor of the immunomodulatory cysteine protease activities in cysticercosis.…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide contributes to host resistance against experimental Taenia crassiceps cysticercosis

et al. 2007

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The immune mechanisms that underlie resistance and susceptibility to cysticercosis are not completely understood. In this paper, using susceptible BALB/c mice and resistant STAT6-/-BALB/c mice, we have analyzed the role of nitric oxide (NO) in determining the outcome of murine cysticercosis caused by the cestode Taenia crassiceps. After T. crassiceps infection, wild-type BALB/c mice developed a strong Th2-like response, produced high levels of IgG1, IgE, IL-5, IL-4, and discrete levels of NO, and remained susceptible to T. crassiceps infection. In contrast, similarly infected BALB/c mice treated with N(omega)-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NO synthase) mounted a similar immune response but with lower levels of NO and harbored nearly 100% more parasites than N(omega)-nitro-D-arginine methyl ester (D-NAME, inactive enantiomer)-treated mice. To further analyze the role of NO in murine cysticercosis, we treated STAT6-/-male mice (known to be highly resistant to T. crassiceps) with L-NAME during 8 weeks of infection. As expected, STAT6-/-mice mounted a strong Th1-like response, produced high levels of IgG2a, IFN-gamma, and IL-17, whereas their macrophages displayed increased transcripts of tumor necrosis factor (TNF)-alpha as well as inducible nitric oxide synthase (iNOS) and efficiently controlled T. crassiceps infection. However, STAT6-/-male mice receiving L-NAME mounted a similar immune response but with lower iNOS transcripts concomitantly with decreased levels of NO in sera and displayed significantly higher parasite burdens. These findings suggest that macrophage activation and NO production are effector mechanisms that importantly contribute in host resistance to T. crassiceps infection. The immune mechanisms that underlie resistance and susceptibility to cysticercosis are not completely understood. In this paper, using susceptible BALB/c mice and resistant STAT6-/-BALB/c mice, we have analyzed the role of nitric oxide (NO) in determining the outcome of murine cysticercosis caused by the cestode Taenia crassiceps. After T. crassiceps infection, wild-type BALB/c mice developed a strong Th2-like response, produced high levels of IgG1, IgE, IL-5, IL-4, and discrete levels of NO, and remained susceptible to T. crassiceps infection. In contrast, similarly infected BALB/c mice treated with N(omega)-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NO synthase) mounted a similar immune response but with lower levels of NO and harbored nearly 100% more parasites than N(omega)-nitro-d-arginine methyl ester (D-NAME, inactive enantiomer)-treated mice. To further analyze the role of NO in murine cysticercosis, we treated STAT6-/-male mice (known to be highly resistant to T. crassiceps) with L-NAME during 8 weeks of infection. As expected, STAT6-/-mice mounted a strong Th1-like response, produced high levels of IgG2a, IFN-gamma, and IL-17, whereas their macrophages displayed increased transcripts of tumor necrosis factor (TNF)-alpha as well as inducible nitric oxide synthase (iNOS) and efficien...

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A cysteine protease from Taenia solium metacestodes induce apoptosis in human CD4+ T-cells

Cited by 41 publications

References 38 publications

The implantation of Taenia solium metacestodes in mice induces down-modulation of T-cell proliferation and cytokine production

The implantation of Taenia solium metacestodes in mice induces down-modulation of T-cell proliferation and cytokine production

Neurocysticercosis: local and systemic immune-inflammatory features related to severity

Nitric oxide contributes to host resistance against experimental Taenia crassiceps cysticercosis

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