RESUMO
Several studies have shown the mechanisms and importance of immune responses against Toxoplasma gondii infection and the notable role of cholinesterases in inflammatory reactions. However, the association between those factors has not yet been investigated. Therefore, the aim of this study was to evaluate the acetylcholinesterase (AChE) activity in blood and lymphocytes and the activity of butyrylcholinesterase (BChE) in serum of rats experimentally infected with T. gondii during the acute phase of infection. For that, an in vivo study was performed with evaluations of AChE and BChE activities on days 5 and 10 post-infection (PI). The activity of AChE in blood was increased on day 5 PI, while in lymphocytes its activity was enhanced on days 5 and 10 PI (P<0.05). No significant difference was observed between groups regarding to the activity of BChE in serum. A positive (P<0.01) correlation was observed between AChE activity and number of lymphocytes. The role of AChE as an inflammatory marker is well known in different pathologies; thus, our results lead to the hypothesis that AChE has an important role in modulation of early immune responses against T. gondii infection.
Assuntos
Acetilcolinesterase/metabolismo , Butirilcolinesterase/metabolismo , Toxoplasma/fisiologia , Toxoplasmose/enzimologia , Acetilcolinesterase/sangue , Animais , Butirilcolinesterase/sangue , Humanos , Linfócitos/enzimologia , Linfócitos/parasitologia , Masculino , Ratos , Ratos Wistar , Toxoplasmose/genética , Toxoplasmose/parasitologiaRESUMO
The induction of indoleamine 2,3-dioxygenase (INDO) expression and the tryptophan (Trp)-kynurenine (Kyn) metabolic pathway during in vivo infection with Toxoplasma gondii was investigated. Decreased levels of Trp and increased formation of Kyn were observed in the lungs, brain, and serum from mice infected with T. gondii. Maximal INDO mRNA expression and enzyme activity were detected in the lungs at 10 to 20 days postinfection. Further, the induction of INDO mRNA expression, Trp degradation and Kyn formation were completely absent in tissues from mice deficient in IFN-gamma (IFN-gamma(-/-)) or IFN regulatory factor -1 (IRF-1(-/-)). These findings indicate the important role of endogenous IFN-gamma and IRF-1 in the in vivo induction of the Trp-Kyn metabolic pathway during acute infection with T. gondii. In contrast, expression of INDO mRNA and its activity was preserved in the tissues of TNF-receptor p55- or inducible nitric oxide synthase-deficient mice infected with T. gondii. Together with the results showing the extreme susceptibility of the IFN-gamma(-/-) and the IRF-1(-/-) mice to infection with T. gondii, our results indicate a possible involvement of INDO and Trp degradation in host resistance to early infection with this parasite.
Assuntos
Proteínas de Ligação a DNA/fisiologia , Expressão Gênica , Interferon gama/fisiologia , Cinurenina/biossíntese , Fosfoproteínas/fisiologia , Toxoplasmose/metabolismo , Triptofano Oxigenase/genética , Triptofano/metabolismo , Doença Aguda , Animais , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/imunologia , Suscetibilidade a Doenças , Fator Regulador 1 de Interferon , Interferon gama/genética , Interferon gama/imunologia , Cinética , Cinurenina/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosfoproteínas/genética , Fosfoproteínas/imunologia , RNA Mensageiro , Toxoplasma/imunologia , Toxoplasmose/enzimologia , Toxoplasmose/imunologia , Triptofano/imunologia , Triptofano Oxigenase/imunologia , Triptofano Oxigenase/metabolismoRESUMO
We assayed mitogen-activated protein (MAP) kinase phosphorylation in a human monocyte cell line (THP1) during their infection by Toxoplasma gondii. In addition, we tested the effect of specific MAP kinase inhibitors (PD098059 and SB203580) on parasite invasion. MAP kinase phosphorylation was increased in the cytosol and membrane fractions of THP1 infected with T. gondii. The MAP kinase phosphorylation of uninfected THP1 cells was not significantly modified by incubation for 20 h with 1000 U/ml of IFN-gamma. However, IFN-gamma treatment of infected cells significantly reduces the increase in phosphorylation caused by parasite infection. There was also MAP kinase activity in the cytosol and membrane fractions of extracellular T. gondii tachyzoites. IFN-gamma altered the distribution of activity in subcellular fractions of extracellular T. gondii tachyzoites. This indicates that IFN-gamma directly affects parasite MAP kinase activity. The results provide evidence that MAP kinase pathways participate in the infection by T. gondii and that the decrease in MAP kinase activity in infected cells caused by IFN-gamma may be involved in mediating their protective signals.
Assuntos
Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Interferon gama/farmacologia , Monócitos/parasitologia , Transdução de Sinais/imunologia , Toxoplasmose/imunologia , Linhagem Celular , Membrana Celular/metabolismo , Citosol/metabolismo , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Interações Hospedeiro-Parasita/efeitos dos fármacos , Humanos , Imidazóis/farmacologia , Monócitos/efeitos dos fármacos , Monócitos/enzimologia , Fosforilação/efeitos dos fármacos , Piridinas/farmacologia , Toxoplasmose/enzimologiaRESUMO
We examined the role of IFN gamma in protection against Toxoplasma gondii in the monocytoid cell line THP1. The addition of IFN gamma to cultured infected THP1 cells reduced the number of parasitized cells without altering intracellular multiplication during the first 24 hr. This reduction was potentiated by bacterial lipopolysaccharide (LPS). We also examined the role of an enzyme important for T. gondii cellular invasion, secretory phospholipase-A2 (sPLA2) and its relation with IFN gamma-induced protection. Treatment of cells or parasites with a specific inhibitor of sPLA2 significantly reduced the number of infected cells at 6 hr. The addition of exogenous sPLA2 from Naja naja venom did not interfere with the protective effect of IFN gamma and conferred protection when used alone. PLA2 activity was measured in supernatants of parasites maintained in the presence of IFN gamma, and the results suggested that IFN gamma opposes cell invasion by T. gondii by suppressing parasite production of PLA2.