Endothelin-1 receptors play a minor role in the protection against acute Trypanosoma cruzi infection in mice

Chagas' disease, caused by the protozoan Trypanosoma cruzi, is a major cause of cardiovascular disability in countries where it is endemic. Damage to the heart microvasculature has been proposed to be an important factor in the pathogenesis of heart dysfunction. Endothelin-1 (ET-1) is a potent vasoconstrictor and exerts its effects via specific ET A and ET B receptors. A few studies have suggested a role for ET-1 and its receptors in the pathogenesis of Chagas' disease. We investigated the effects of treatment with bosentan, an ET A/ET B receptor antagonist, on the course of T. cruzi infection (Y strain) in C57Bl/6 mice. Treatment with bosentan (100 mg kg-1 day-1) was given per os starting day 0 after infection until sacrifice. Bosentan significantly increased myocardial inflammation, with no effects on parasitemia. Although the total number of nests was similar, a lower number of intact amastigote nests was found in the heart of bosentan-treated animals. Bosentan failed to affect the infection-associated increase in the cardiac levels of the cytokines IFN-g and TNF-a and the chemokines CCL2/MCP-1, CCL3/MIP-1a and CCL5/RANTES. In vitro, pre-incubation with ET-1 (0.1 æM) 4 h before infection enhanced the uptake of the parasites by peritoneal macrophages, and this effect was abrogated when macrophages were pre-treated with bosentan (1 æM) 15 min before incubation with ET-1. However, ET-1 did not alter killing of intracellular parasites after 48 h of in vitro infection. Our data suggest that bosentan-treated mice have a delay in controlling parasitism which is compensated for exacerbated inflammation. Infection is eventually controlled in these animals and lethality is unchanged, demonstrating that ET-1 plays a minor role in the protection against acute murine T. cruzi infection.

Lepra: evaluación inmunonológica de contactos intradomiciliarios / Leprosy: an assessment of contacts inmunonológica intradomiciliary

Los contactos intradomiciliarios de pacientes con lepra representan una población con riesgo de infección . El uso combinado de pruebas cutáneas y ELISA revela el grado de sensibilización, la capacidad de respuesta inmunológica y casos subclínicos de la enfermedad. Con base en lo anteriormente expuesto y con la finalidad de justificar el uso de estas pruebas, de rutina en otros contactos, se entrevistó el evaluó clínicamente a 211 contactos intradomiciliarios, de 32 casos de lepra registrados. Se colocó a los contactos lepramina intradérmica y se determinó niveles de anticuerpos específicos contra M. leprae (prueba de ELISA con PGL-1). De la población evaluada, 99.88 por ciento presentó reacción de Fernández negativa y 2/3 de ella presentó una reacción de Mitsuda positiva. Sólo 30.85 por ciento constituyó un grupo de riesgo por presentar reacción de Mitsuda negativa. Al correlacionar las pruebas cutáneas con el ELISA se mostró que ninguno presentaba lepra en fase subclínica y que un sólo caso de ELISA débilmente positivo resultó ser una infección pasada autolimitada. No se justifica usar todas las pruebas inmunológicas, en todos los contactos. Se recomienda usar pruebas cutáneas para detectar grupos de riesgo y para orientar quimiprofilaxis, reservado el uso del ELISA sólo para grupos de riesgo demostrado.

Expression of extracellular matrix components and their receptors in the central nervous system during experimental Toxoplasma gondii and Trypanosoma cruzi infection

Alterations in extracellular matrix (ECM) expression in the central nervous system (CNS) usually associated with inflammatory lesions have been described in several pathological situations including neuroblastoma and demyelinating diseases. The participation of fibronectin (FN) and its receptor, the VLA-4 molecule, in the migration of inflammatory cells into the CNS has been proposed. In Trypanosoma cruzi infection encephalitis occurs during the acute phase, whereas in Toxoplasma infection encephalitis is a chronic persisting process. In immunocompromised individuals such as AIDS patients, T. cruzi or T. gondii infection can lead to severe CNS damage. At the moment, there are no data available regarding the molecules involved in the entrance of inflammatory cells into the CNS during parasitic encephalitis. Herein, we characterized the expression of the ECM components FN and laminin (LN) and their receptors in the CNS of T. gondii- and T. cruzi-infected mice. An increased expression of FN and LN was detected in the meninges, leptomeninges, choroid plexus and basal lamina of blood vessels. A fine FN network was observed involving T. gondii-free and T. gondii-containing inflammatory infiltrates. Moreover, perivascular spaces presenting a FN-containing filamentous network filled with Alpha 4+ and Alpha 5+ cells were observed. Although an increased expression of LN was detected in the basal lamina of blood vessels, the CNS inflammatory cells were alpha 6-negative. Taken together, our results suggest that FN and its receptors VLA-4 and VLA-5 might be involved in the entrance, migration and retention of inflammatory cells into the CNS during parasitic infections