The Experts below are selected from a list of 294 Experts worldwide ranked by ideXlab platform
Dirk Schluter - One of the best experts on this subject based on the ideXlab platform.
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the induction and kinetics of antigen specific cd8 t cells are defined by the stage specificity and compartmentalization of the antigen in Murine Toxoplasmosis
Journal of Immunology, 2003Co-Authors: Laiyu Kwok, Sonja Lutjen, Sabine Soltek, Dominique Soldati, Dirk H Busch, Martina Deckert, Dirk SchluterAbstract:Toxoplasma gondii forms different life stages, fast-replicating tachyzoites and slow-growing bradyzoites, in mammalian hosts. CD8 T cells are of crucial importance in Toxoplasmosis, but it is unknown which parasite stage is recognized by CD8 T cells. To analyze stage-specific CD8 T cell responses, we generated various recombinant Toxoplasma gondii expressing the heterologous Ag β-galactosidase (β-gal) and studied whether 1) secreted or cytoplasmic Ags and 2) tachyzoites or bradyzoites, which persist intracerebrally, induce CD8 T cells. We monitored the frequencies and kinetics of β-gal-specific CD8 T cells in infected mice by MHC class I tetramer staining. Upon oral infection of B6C (H-2bxd) mice, only β-gal-secreting tachyzoites induced β-gal-specific CD8 T cells. However, upon secondary infection of mice that had received a primary infection with tachyzoites secreting β-gal, β-gal-secreting tachyzoites and bradyzoites transiently increased the frequency of intracerebral β-gal-specific CD8 T cells. Frequencies of splenic and cerebral β-gal-specific CD8 T cells peaked at day 23 after infection, thereafter persisting at high levels in the brain but declining in the spleen. Splenic and cerebral β-gal-specific CD8 T cells produced IFN-γ and were cytolytic upon specific restimulation. Thus, compartmentalization and stage specificity of an Ag determine the induction of CD8 T cells in Toxoplasmosis.
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crucial role of tnf receptor type 1 p55 but not of tnf receptor type 2 p75 in Murine Toxoplasmosis
Journal of Immunology, 1998Co-Authors: M Deckertschluter, Horst Bluethmann, Andrea Rang, Dirk SchluterAbstract:TNF-α exerts its biologic activity through two distinct receptors, TNF receptor type 1 (TNFR1, p55) and TNF receptor type 2 (TNFR2, p75). To analyze their function in Toxoplasmosis, we orally infected mice genetically deficient for TNFR1 (TNFR1 0/0 ), TNFR2 (TNFR2 0/0 ), or both TNF receptors (TNFR1/2 0/0 ), as well as wild-type (wt) mice with a low-virulent strain of Toxoplasma gondii . TNFR1/2 0/0 and TNFR1 0/0 mice succumbed to Toxoplasmosis within 17 and 27 days, respectively, whereas TNFR2 0/0 and wt mice were equally resistant to acute Toxoplasmosis. Histopathology attributed death of TNFR1/2 0/0 and TNFR1 0/0 mice to a fulminant necrotizing encephalitis. In addition, pneumonia contributed to the fatal outcome. The poor prognosis of TNFR1/2 0/0 and TNFR1 0/0 mice was reflected by a significantly increased parasitic load in the brain and lung as compared with TNFR2 0/0 and wt mice. Immunohistochemistry demonstrated a remarkable reduction of inducible nitric oxide synthase protein in brain and lung of TNFR1/2 0/0 and TNFR1 0/0 as compared with TNFR2 0/0 and wt mice. Reverse-transcribed PCR showed that in contrast to TNFR2 0/0 and wt mice, TNFR1 0/0 mice were unable to up-regulate inducible nitric oxide synthase mRNA transcripts in the course of infection, whereas intracerebral levels of IFN-γ, TNF-α, and IL-1β mRNA transcripts, recruitment of immune cells to the brain, and the amount of apoptotic cells in inflammatory foci did not differ significantly among the various experimental groups. These results illustrate that in Toxoplasma encephalitis, TNF-α-mediated immune responses are of crucial importance and that signaling through TNFR1, but not TNFR2, provides the stimulus required for the induction of protective nitric oxide.
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Toxoplasma encephalitis in congenic B10 and BALB mice: impact of genetic factors on the immune response.
Infection and Immunity, 1994Co-Authors: Martina Deckert-schlüter, Dirk Schluter, G. Schwendemann, D. Schmidt, Otmar D. WiestlerAbstract:Factors which determine the pathogenesis and course of Toxoplasma encephalitis are poorly understood. In the present study, the influence of genetic factors in congenic B10 and BALB mice of H-2q, H-2k, and H-2b haplotypes was examined following oral infection with a low-virulence strain of Toxoplasma gondii (DX). There were striking differences among these strains. Whereas B10 mice were highly susceptible, BALB mice had a less severe and more protracted disease. In all animals with a fatal outcome, Toxoplasma encephalitis was the cause of death. Within the two congenic groups, the major histocompatibility complex haplotype had a strong impact on the disease. The H-2k haplotype was associated with early death in B10 mice but with a favorable outcome in BALB mice, whereas the reverse was observed for the H-2q haplotype. These findings indicate that genetically determined factors are critically involved in determining the intracerebral immune response and the course of Murine Toxoplasmosis. Some of these factors appear to be associated with the major histocompatibility complex haplotype, but significant differences between B10 and BALB mice point to a modulating role of additional genetic loci. Immunohistochemical studies and cytokine analyses of cerebrospinal fluid and serum revealed significant differences in the intracerebral immune response between susceptible and resistant strains. A poor outcome was associated with a large number of intracerebral parasites, significant tissue necrosis, a reduced number of intracerebral CD4+ T cells, low intrathecal tumor necrosis factor levels, and, to a lesser extent, a reduced number of intracerebral CD8+ T cells.
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Expression of major histocompatibility complex class II antigens and levels of interferon-gamma, tumour necrosis factor, and interleukin-6 in cerebrospinal fluid and serum in Toxoplasma gondii-infected SCID and immunocompetent C.B-17 mice.
Immunology, 1993Co-Authors: Dirk Schluter, Martina Deckert-schlüter, G. Schwendemann, H. BrunnerAbstract:: In order to investigate activation of the innate immune system in Murine Toxoplasmosis, T- and B-cell-deficient SCID mice and their co-isogenic immunocompetent C.B-17 counterparts were orally infected with a low-virulent strain of Toxoplasma gondii (DX strain). SCID mice developed a fatal necrotizing Toxoplasmosis, whereas CD4+ and CD8+ T cells contributing to inflammatory infiltrates conferred resistance to immunocompetent mice. Significant amounts of interferon-gamma (IFN-gamma) were detectable in SCID mice. The most likely source for this cytokine is activated natural killer (NK) cells. In comparison to immunocompetent mice IFN-gamma levels were reduced in cerebrospinal fluid (CSF) and serum of SCID mice at days 7 and 14 of disease. Similar amounts of tumour necrosis factor (TNF) were detected in both strains of mice. In addition, immunohistochemistry showed major histocompatibility complex (MHC) class II antigen expression on SCID and C.B-17 microglial cells and macrophages demonstrating activation of these cells in both strains. However, the up-regulation of MHC class II antigen on microglia was less pronounced in SCID mice, presumably due to reduced levels of IFN-gamma. Interleukin-6 (IL-6) levels in CSF and serum were elevated in both strains and correlated with systemic and intracerebral disease activity. In conclusion, our results demonstrate activation of macrophages and NK cells as the predominant defence mechanisms of the comprised SCID immune system during toxoplasma infection. This implies a major role for the innate immune system during early stages of Toxoplasmosis although T cells are necessary to control the infection efficiently.
Jack S Remington - One of the best experts on this subject based on the ideXlab platform.
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activity of trovafloxacin in combination with other drugs for treatment of acute Murine Toxoplasmosis
Antimicrobial Agents and Chemotherapy, 1997Co-Authors: A A Khan, Fausto G Araujo, T Slifer, R J Polzer, Jack S RemingtonAbstract:Current therapy for Toxoplasmosis with a synergistic combination of pyrimethamine plus sulfadiazine or pyrimethamine plus clindamycin is not always efficacious and is frequently discontinued due to intolerable toxic effects in immunocompromised individuals, particularly those with AIDS. Trovafloxacin, a new fluoroquinolone with potent activity against Toxoplasma gondii, was examined for potential synergistic activity when combined with other drugs used for treatment of human Toxoplasmosis. Combinations of trovafloxacin with clarithromycin, pyrimethamine, or sulfadiazine demonstrated significantly enhanced activities compared to those observed with each drug alone. Our results suggest that combinations of trovafloxacin and other anti-toxoplasma drugs should be further explored for treatment of Toxoplasmosis in humans.
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Treatment with interleukin 12 in combination with atovaquone or clindamycin significantly increases survival of mice with acute Toxoplasmosis.
Antimicrobial Agents and Chemotherapy, 1997Co-Authors: Fausto G Araujo, Christopher A. Hunter, Jack S RemingtonAbstract:The capacity of interleukin 12 (IL-12) to potentiate drugs in the treatment of Murine Toxoplasmosis was examined. IL-12 (100 ng/injection), atovaquone (10 mg/kg of body weight/day), or clindamycin (5 mg/kg/day) administered alone caused delayed time to death or minimal survival rates. In contrast, significant survival rates resulted when the same dose of IL-12 was used in combination the same doses of atovaquone (P=0.01) or clindamycin (P=0.001). Infected mice treated with IL-12 plus drug produced significantly higher levels of gamma interferon than controls. Although IL-12 was effective only when administered before infection, these results suggest that this cytokine may be a useful adjunct in the therapy of human Toxoplasmosis in situations when cysts reactivate and tachyzoites start multiplying in immunocompromised patients.
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studies on the role of interleukin 12 in acute Murine Toxoplasmosis
Immunology, 1995Co-Authors: C A Hunter, Ermanno Candolfi, C S Subauste, V Van Cleave, Jack S RemingtonAbstract:: Interleukin-12 (IL-12) is important in the regulation of resistance to Toxoplasma gondii in mice with severe combined immunodeficiency (SCID). The protective ability of IL-12 in SCID mice appears to be through its activity on natural killer (NK) cells to induce production of interferon-gamma (IFN-gamma). In this study we assessed the role of IL-12 in the acute stage of Toxoplasmosis in immunocompetent mice. Administration of IL-12 to BALB/c mice infected with the virulent C56 strain of T. gondii remarkably delayed time to death. The protective activity of IL-12 was abrogated by administration of monoclonal antibodies to IFN-gamma or tumour necrosis factor-alpha (TNF-alpha), and by depletion of NK cells using an antisera against asialoGM1. Whereas BALB/c mice infected with the ME49 strain of T. gondii survived infection, administration of anti-IL-12 to infected mice resulted in 100% mortality accompanied by decreased serum levels of IFN-gamma. Furthermore, this treatment significantly reversed the suppression of spleen cell proliferation to concanavalin A (Con A), which is associated with the acute stage of infection, and resulted in decreased ex vivo production of IFN-gamma, IL-2, IL-4 and IL-10 in response to Con A. Our results indicate an important role for IL-12 in mediating resistance to T. gondii during acute infection in immunocompetent mice, that NK cells are required for this protective activity, and that IL-12 is involved in the immunosuppression which accompanies this infection.
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mitogen and antigen specific proliferation of t cells in Murine Toxoplasmosis is inhibited by reactive nitrogen intermediates
Infection and Immunity, 1994Co-Authors: Ermanno Candolfi, C A Hunter, Jack S RemingtonAbstract:Acute and chronic infections with Toxoplasma gondii result in a nonspecific suppression of immunologic function in mice and humans. Proliferation of spleen cells in response to concanavalin A (ConA) and toxoplasma lysate antigen (TLA) was studied during the course of infection in mice susceptible (CBA/Ca) and resistant (BALB/c) to development of toxoplasmic encephalitis to determine if reactive nitrogen intermediates (RNI) are involved in the suppression of the proliferative responses. Maximal suppression of proliferation of spleen cells in response to ConA and TLA was observed on days 7 and 14 after infection and correlated with elevated levels of nitrite in spleen cell culture supernatants. By day 68 postinfection in BALB/c mice, proliferative responses returned to normal levels, whereas in CBA/Ca mice, they remained suppressed. The addition of an inhibitor of production of RNI (NG-monomethyl-L-arginine) increased proliferation of spleen cells in response to both ConA and TLA at days 7, 14, and 21 after infection. Depletion of adherent cells from spleen cell preparations obtained from acutely infected mice followed by their repletion with adherent spleen cells from uninfected mice resulted in increased proliferation of spleen cells from infected mice and a significant decrease in nitrite in the cultures. These results indicate that production of RNI by macrophages contributes significantly to the suppression of the spleen cell proliferation observed in the acute stage of Toxoplasmosis.
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the activity of atovaquone 566c80 in Murine Toxoplasmosis is markedly augmented when used in combination with pyrimethamine or sulfadiazine
The Journal of Infectious Diseases, 1993Co-Authors: Fausto G Araujo, Jack S RemingtonAbstract:: The activity of atovaquone in the treatment of Murine Toxoplasmosis was greatly enhanced when administered in combination with pyrimethamine or sulfadiazine. Mice infected with lethal inocula of tachyzoites or cysts of Toxoplasma gondii and treated with doses of atovaquone, pyrimethamine, or sulfadiazine that were ineffective when administered alone had 70% survival when pyrimethamine plus atovaquone and 100% survival when sulfadiazine plus atovaquone was used. Of interest, doses of pyrimethamine and, particularly, sulfadiazine far below the doses that would induce any protection in infected mice were active when combined with atovaquone. These results suggest that clinical trials for treatment of Toxoplasmosis in AIDS patients using the combination of atovaquone with sulfadiazine or pyrimethamine are justified.
Ahmad Daryani - One of the best experts on this subject based on the ideXlab platform.
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Survey on synergism effect of ketotifen in combination with pyrimethamine in treatment of acute Murine Toxoplasmosis
Tropical Medicine and Health, 2017Co-Authors: Mahbobeh Montazeri, Mohammad Ali Ebrahimzadeh, Ehsan Ahmadpour, Mehdi Sharif, Shahabeddin Sarvi, Kian Rezaei, Mohammad Taghi Rahimi, Abdol Satar Pagheh, Saeed Mehrzadi, Ahmad DaryaniAbstract:Background Standard treatment of Toxoplasmosis is accompanied by severe side effects and low tolerability; accordingly, alternative medicines are critically needed. Ketotifen (KET) as a cell membrane stabilizer could be an appropriate inhibitor of Toxoplasma gondii ( T. gondii ) parasite entrance into the host cells. Therefore, the focus of current study is characterization of the anti- Toxoplasma activity of KET in the acute phase of Toxoplasmosis in Murine model as pre-treatment and post-treatment (before and after infection with RH strain). KET was used intraperitoneally both individually (2 and 3 mg/kg/day) and in combination with pyrimethamine (PYR) (50 mg/kg/day). One week after the post infection, DNA was extracted from brain biopsies samples. Parasite load was calculated using Quantitative-PCR (Q-PCR) in a triplicate reaction for each DNA with the target for at RE (a 529 bp repeat element) gene. Results A significant difference between KET and control groups was observed ( P
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survey on synergism effect of ketotifen in combination with pyrimethamine in treatment of acute Murine Toxoplasmosis
Tropical Medicine and Health, 2017Co-Authors: Mahbobeh Montazeri, Mohammad Ali Ebrahimzadeh, Ehsan Ahmadpour, Mehdi Sharif, Shahabeddin Sarvi, Kian Rezaei, Mohammad Taghi Rahimi, Abdol Satar Pagheh, Saeed Mehrzadi, Ahmad DaryaniAbstract:Background Standard treatment of Toxoplasmosis is accompanied by severe side effects and low tolerability; accordingly, alternative medicines are critically needed. Ketotifen (KET) as a cell membrane stabilizer could be an appropriate inhibitor of Toxoplasma gondii (T. gondii) parasite entrance into the host cells. Therefore, the focus of current study is characterization of the anti-Toxoplasma activity of KET in the acute phase of Toxoplasmosis in Murine model as pre-treatment and post-treatment (before and after infection with RH strain). KET was used intraperitoneally both individually (2 and 3 mg/kg/day) and in combination with pyrimethamine (PYR) (50 mg/kg/day). One week after the post infection, DNA was extracted from brain biopsies samples. Parasite load was calculated using Quantitative-PCR (Q-PCR) in a triplicate reaction for each DNA with the target for at RE (a 529 bp repeat element) gene.
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Evaluation of Propranolol Effect on Experimental Acute and Chronic Toxoplasmosis Using Quantitative PCR.
Antimicrobial Agents and Chemotherapy, 2016Co-Authors: Mahbobeh Montazeri, Mohammad Ali Ebrahimzadeh, Ehsan Ahmadpour, Mehdi Sharif, Shahabeddin Sarvi, Ahmad DaryaniAbstract:: Current therapies against Toxoplasmosis are limited, and drugs have significant side effects and low efficacies. We evaluated the potential anti-Toxoplasma activity of propranolol at a dose of 2 or 3 mg/kg of body weight/day in vivo in the acute and chronic phases. Propranolol as a cell membrane-stabilizing agent is a suitable drug for inhibiting the entrance of Toxoplasma gondii tachyzoites into cells. The acute-phase assay was performed using propranolol, pyrimethamine, and propranolol plus pyrimethamine before (pretreatment) and after (posttreatment) intraperitoneal challenge with 1 × 103 tachyzoites of the virulent T. gondii strain RH in BALB/c mice. Also, in the chronic phase, treatment was performed 12 h before intraperitoneal challenge with 1 × 106 tachyzoites of the virulent strain RH of T. gondii in rats. One week (in the acute phase) and 2 months (in the chronic phase) after postinfection, tissues were isolated and DNA was extracted. Subsequently, parasite load was calculated using quantitative PCR (qPCR). In the acute phase, in both groups, significant anti-Toxoplasma activity was observed using propranolol (P < 0.001). Propranolol in the pretreatment group showed higher anti-Toxoplasma activity than propranolol in posttreatment in brain tissues, displaying therapeutic efficiency on Toxoplasmosis. Also, propranolol combined with pyrimethamine reduced the parasite load as well as significantly increased survival of mice in the pretreatment group. In the chronic phase, anti-Toxoplasma activity and decreased parasite load in tissues were observed with propranolol. In conclusion, the presented results demonstrate that propranolol, as an orally available drug, is effective at low doses against acute and latent Murine Toxoplasmosis, and the efficiency of the drug is increased when it is used in combination therapy with pyrimethamine.
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effect of propranolol alone and in combination with pyrimethamine on acute Murine Toxoplasmosis
Jundishapur Journal of Microbiology, 2015Co-Authors: Mahbobeh Montazeri, Ahmad Daryani, Mohammad Ali Ebrahimzadeh, Ehsan Ahmadpour, Mehdi Sharif, Shahabeddin SarviAbstract:Objectives: In this study, we investigated the anti-Toxoplasma gondii efficacy of propranolol in vivo. Materials and Methods: This study was performed in two separate pre-treatment and post-treatment groups. In each group, 18 female Balb/c mice in six subgroups (n = 3) were used to assess the anti-Toxoplasma effect of propranolol at 2 and 3 mg/kg/day, pyrimethamine at 50 mg/kg/day, propranolol at 2 and 3 mg/kg/day plus pyrimethamine, and phosphate-buffered saline (PBS; as negative control). Treatment was performed 4, 24, and 48 hours before and after an intraperitoneal challenge of 1 × 10 3 tachyzoites of the virulent RH strain of T. gondii, in pre-treatment and post-treatment groups. Mice peritoneal exudates were collected on the seventh day after the challenge and parasite numbers were recorded as percent of growth inhibition and survival rate. Results: In the pre-treatment group, results showed that propranolol at 2 and 3 mg/kg combined with pyrimethamine was more effective in inhibiting growth of tachyzoites (86% and 98%, respectively) when compared with propranolol at 2 and 3 mg/kg (37% and 39%, respectively) and pyrimethamine (41%) alone. In the post-treatment group, all combined treatments significantly reduced parasite load. The growth inhibition of tachyzoites in mice receiving propranolol (2 and 3 mg/kg) was 75% and 51%, with the mean tachyzoites count being 1526 ± 171.4 and 2948 ± 1452.8, respectively, compared with pyrimethamine treatment outcome, which represents 99.9% growth inhibition. Conclusions: Our results demonstrated the promising prophylactic and therapeutic effects of propranolol against T. gondii infection. Propranolol also increases the efficacy of pyrimethamine in combination therapies.
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determination of parasitic load in different tissues of Murine Toxoplasmosis after immunization by excretory secretory antigens using real time qpcr
Experimental Parasitology, 2014Co-Authors: Ahmad Daryani, Ehsan Ahmadpour, Mehdi Sharif, Shahabeddin Sarvi, Yousef Dadimoghaddam, Mohammad Bagher Hashemi Souteh, Alireza Khalilian, Touraj Farazmand, Hamed Kalani, Mehdi RasouliAbstract:Abstract Excretory–secretory antigens (ESAs) of Toxoplasma gondii are one of the candidates for immunization against Toxoplasmosis. For evaluation of immunization, we determined the kinetics of the distribution of Toxoplasma and parasite load in different tissues of mice immunized by ESAs. In this experimental study, 36 mice in case (n = 18) and control (n = 18) groups were immunized with ESAs and PBS, respectively. After 2 weeks, mice were challenged intraperitoneally with Toxoplasma virulent RH strain. Blood and different tissues (brain, spleen, liver, heart, kidney, and muscle) were collected daily after challenge (1, 2, 3 and last day before death). Parasite load was calculated using Real time QPCR targeted at the B1 gene. ESAs as vaccine in different tissues showed various effects. However, infected mice which received the vaccine in comparison with control group, displayed a drastically decreasing in parasite burden, in their blood and tissues (P = 0.000). These results indicated that ESAs with reduction of parasite load in different tissues of host could be evaluable candidate for the development of immunization strategies against Toxoplasmosis.
Denis Richard - One of the best experts on this subject based on the ideXlab platform.
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induction of ucp2 expression in brain phagocytes and neurons following Murine Toxoplasmosis an essential role of ifn γ and an association with negative energy balance
Journal of Neuroimmunology, 2007Co-Authors: Denis Arsenijevic, Sebastien Clavel, Daniel Sanchis, Julie Plamondon, Quingling Huang, Daniel Ricquier, Laurie Rouger, Denis RichardAbstract:Abstract A model of Murine Toxoplasmosis was used to study cellular and temporal expression of uncoupling protein-2 (Ucp2) in the brain. In situ hybridization indicated that Ucp2 was located in neurons. Nuclei structures involved in energy balance, in particular the nucleus of the solitary tract (NST), was shown to have a positive association between negative energy balance and Ucp2 levels. Infection-induced Ucp2 expression colocalized mainly with microglial cells, but also with infiltrating macrophages and neutrophils in the brain, which was evident from day 9 post-infection. Using cytokine knockout mice we demonstrate that microglial Ucp2 induction in the brain was largely dependant on interferon-γ, but not interleukin-6 or tumour-necrosis-factor-α in response to infection. In summary, this study shows that Ucp2 is regulated in a different manner in neurons than in microglia/phagocytes following infection. Our study indicates that an association exists between negative energy balance and neuronal Ucp2 levels in the NST, in particular.
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Induction of Ucp2 expression in brain phagocytes and neurons following Murine Toxoplasmosis: an essential role of IFN-gamma and an association with negative energy balance.
Journal of neuroimmunology, 2007Co-Authors: Denis Arsenijevic, Sebastien Clavel, Daniel Sanchis, Julie Plamondon, Quingling Huang, Daniel Ricquier, Laurie Rouger, Denis RichardAbstract:A model of Murine Toxoplasmosis was used to study cellular and temporal expression of uncoupling protein-2 (Ucp2) in the brain. In situ hybridization indicated that Ucp2 was located in neurons. Nuclei structures involved in energy balance, in particular the nucleus of the solitary tract (NST), was shown to have a positive association between negative energy balance and Ucp2 levels. Infection-induced Ucp2 expression colocalized mainly with microglial cells, but also with infiltrating macrophages and neutrophils in the brain, which was evident from day 9 post-infection. Using cytokine knockout mice we demonstrate that microglial Ucp2 induction in the brain was largely dependant on interferon-gamma, but not interleukin-6 or tumour-necrosis-factor-alpha in response to infection. In summary, this study shows that Ucp2 is regulated in a different manner in neurons than in microglia/phagocytes following infection. Our study indicates that an association exists between negative energy balance and neuronal Ucp2 levels in the NST, in particular.
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a role for interferon gamma in the hypermetabolic response to Murine Toxoplasmosis
European Cytokine Network, 2001Co-Authors: Denis Arsenijevic, Fabienne De Bilbao, Panteleimon Giannakopoulos, Lucien Girardier, Sonia Samec, Denis RichardAbstract:INTRODUCTION Infection may result in a wide array of alterations in metabolic activity, which when severe, may lead to a hypermetabolic state eventually leading to the loss of body weight. Peripheral and especially central cytokine expressions are believed to be of importance in infection induced hypermetabolism [1-3]. The effect of central cytokines has been mainly studied in short term protocols using cytokine or bacterial lipopolysaccharide [...]
Y. Kaneda - One of the best experts on this subject based on the ideXlab platform.
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multiple organ dysfunction in congenital Murine Toxoplasmosis
The Tokai journal of experimental and clinical medicine, 2004Co-Authors: W. Stahl, M. Sekiguchi, Y. KanedaAbstract:Infection of gravid Nya: NYLAR (NYLAR), C57BL/6J (C57), and BALB/c mice with Toxoplasma gondii, on gestation day 7, resulted in fetal resorptions, abortions, and still-births. Fetal wastage (estimated) was 35 and 40 % in the NYLAR and C57 strains and 55 % in the BALB/c strain. Postnatally, pups were cachectic and growth-retarded, with some developing hind limb weakness, petechial lesions on ears and tail, and a blood-tinged nasal exudate. Only 13 of 97 BALB/c pups, 14 of 41 C57 pups, and 46 of 153 NYLAR pups survived the first month of life. At necropsy, swollen, blotched livers, enlarged spleens, pallid kidneys and pulmonary hemorrhages were observed. Cysts of T. gondii were detected in every pup, via press-smears of brain. Histologic examination revealed mineralizing cavitations, ventricular deformations, and periventricular edema in the central nervous system; extensive liver pathology marked by hepatocellular necrosis and calcification, sinusoidal dilatation, and giant cell granulomas; congestion of the spleen with blurring of red and white compartments and cavitations in the white pulp; and tubule and glomerular necrosis and calcification in the kidney. The pulmonary hemorrhages and dermal petechial lesions may reflect a bleeding diathesis due to hepatic insufficiency. The pathogenesis of congenital Toxoplasmosis, in the 3 strains of mice, appears due to microvascular dysfunction characterized by dysregulation of hemostasis, perfusion failure, and multiple organ dysfunction, rather than to parasite-mediated cytopathology. We suggest that hematogenous dissemination and endothelial invasion by the parasite induced a systemic inflammatory response syndrome (i.e; toxoplasmic sepsis) leading to the microvascular dysfunction.
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Cerebellar anomalies in congenital Murine Toxoplasmosis
Parasitology Research, 2002Co-Authors: W. Stahl, M. Sekiguchi, Y. KanedaAbstract:Gravid Nya:NYLAR mice, infected with Toxoplasma gondii on gestation day 7, experienced embryo resorptions, abortions, stillbirths, and a reduction in average litter size by one-third. Postnatally, all congenitally infected pups showed growth retardation, cachexia, and hind limb weakness. Some pups developed necrotic petechiae on the ears and tail, and a blood-tinged nasal discharge. Coronal sections of the cerebellum at age 1 month revealed developmental abnormalities including: persistence of remnants of an external granular layer; fragmented and disoriented Bergmann glial foot processes; numerous ectopic granule cells stranded in the molecular layer; focal disorganization and edema of the Purkinje cell layer; and thinning of the internal granular layer. Our working hypothesis is that the cerebellar anomalies originated with parasite invasion of the fetal vascular endothelium leading to vasculitis and microcirculatory dysfunction, perivascular edema, perfusion impairment, and tissue anoxia. In the cerebellar folia, the cellular migration defects are attributed to edema-induced swelling and fragmentation of the Bergmann glial foot processes that guide migrating neurons, whereas the focal loss of Purkinje and granule cells is ascribed to hypoxia–ischemia. Although Toxoplasma cysts were detected in the cerebellum, morphologic evidence of parasite association with neuropathology was not obtained.
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cerebral anomalies in congenital Murine Toxoplasmosis a preliminary report
The Tokai journal of experimental and clinical medicine, 1998Co-Authors: W. Stahl, Y. KanedaAbstract:: Gravid Nya: NYLAR strain mice were infected with Toxoplasma gondii on embryonic day 7. During the remaining 12 days of gestation, considerable fetal wastage occurred. At birth, pups were sickly and growth-stunted, and postnatal mortality was high. After 1 month, surviving weanlings were killed and autopsied. Coronal sections of the cerebrum revealed: numerous cortical and periventricular cystic cavitations, some undergoing calcification; ventricular enlargement and marked periventricular edema; subependymal nodules bulging into the ventricles; loss of subependymal germinal cells; and meningeal and perivascular inflammation. We suggest, as a working hypothesis, that hematogenously transported parasites invaded the vascular endothelium of the fetal cerebrum, inducing endothelial cell activation, recruitment of inflammatory cells, and focal inflammatory lesions in the endothelium. These inflammatory lesions triggered an intravascular coagulopathy, leading to the formation and deposition of microthrombi in cerebral capillaries and the development of numerous infarcts. Hypoxic-ischemic necrosis of the infarcted tissues led to the creation of the cystic cavitations.
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impaired thyroid function in Murine Toxoplasmosis
Parasitology, 1998Co-Authors: W. Stahl, Y. KanedaAbstract:A decline in serum thyroxine (T 4 ) occurs in Nya[ratio ]NYLAR female mice infected with Toxoplasma gondii . To ascertain whether the hypothyroxinaemia might be the result of primary thyroid dysfunction, 2 parameters of thyrofollicular cell function were monitored to determine (a) if the cell surface membrane receptors for thyroid-stimulating hormone (TSH) were operative, and (b) whether the cyclic adenosine monophosphate (cAMP)-dependent cascade of intracellular events leading to the release of T 4 was responsive to exogenous cAMP. Our results indicated that both parameters were intact and functional in the infected-mouse thyrocytes. However, the elicited T 4 responses were distinctly diminished in magnitude, reflecting a lack of readily available thyroidal T 4 reserves. Because the continuing synthesis, storage, and release of T 4 is dependent on the pulsatile stimulation of the thyroid by TSH, we suggest that the depletion of T 4 reserves is likely due to perturbation of the pulsatile release of TSH from the pituitary, rather than to primary thyroid malfunction.
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aetiology of thyroidal dysfunction in Murine Toxoplasmosis
Parasitology, 1998Co-Authors: W. Stahl, Y. KanedaAbstract:: Mice infected with Toxoplasma gondii manifest a rapid decline in serum thyroxine (T4) levels. To locate the locus of the hypothyroxinaemia, the integrity of the pituitary-thyroid axis of infected mice was assessed by a thyrotropin-releasing hormone (TRH) assay. A rise in serum T4 after inoculation of TRH implies the release of thyrotropin (thyroid-stimulating hormone) from a functionally intact pituitary. Administration of a single, large-dose (1 microgram) bolus of TRH to infected mice induced a positive, although subnormal, T4 response. In contrast, when infected mice were pre-treated with a series of low-dose (5 ng) pulses of TRH prior to the bolus challenge, the T4 response was markedly enhanced. We suggest that the multiple inoculations of low-dose pulses of TRH 'primed' the pituitary (and secondarily the thyroid) and led to replenishment of their readily available hormone reserves and the heightened response to stimulation. These observations indicate that the locus of thyroid dysfunction is in the hypothalamus, not the pituitary or thyroid, and apparently involves impairment of the pulsatile release of TRH.
