Role of Arachidonic acid metabolites in Trypanosoma cruzi infection

• Autores: Nestos Adrián Guerrero Gutiérrez
• Directores de la Tesis: Manuel Fresno Escudero (dir. tes.), Núria Gironés Pujol (dir. tes.)
• Lectura: En la Universidad Autónoma de Madrid ( España ) en 2013
• Idioma: inglés
• Tribunal Calificador de la Tesis: Carlos Alonso Bedate (presid.), Manuel Soto Álvarez (secret.), Julien Santi Rocca (voc.), Paloma Martín Sanz (voc.), Luis Vila Navarro (voc.)
• Materias:
  • Ciencias de la vida
    • Biología molecular
• Enlaces
  • Tesis en acceso abierto en: Biblos-e Archivo
• Resumen

  • In Chagas disease, caused by Trypanosoma cruzi, inflammation plays an important role in the pathophysiology. Lipid mediators derived from arachidonic acid (AA), as prostaglandins and leukotrienes, are considered regulators of homeostasis and inflammation. These molecules are produced by a biosynthetic pathway controlled by enzymes as cyclooxygenases and lipoxygenases. The role of cyclooxygenase-2 (COX-2) in immunosuppression during the acute phase of T. cruzi infection has been described using non-steroidal anti-inflammatory drugs, which are inhibitors of this enzyme. In this study, we first investigated the expression of enzymes involved in AA metabolism during T. cruzi infection. Susceptible and nonsusceptible models of infection were used to further analyze the role of lipid mediators in T. cruzi infection. Our results confirm the expression of several of these enzymes in T. cruzi infected heart, in particular COX-2. CD68+ heart-infiltrating macrophages were the major cell type expressing COX-2. CD11b+ heart-infiltrating myeloid cells were purified and produced prostaglandins PGE2 and PGF2¿. In contrast, no AA metabolite was produced by the parasite itself. Studies using gene-deficient animal models indicate that regulation of COX-2 and PGE2 (through Prostaglandin E receptor 2 signaling) is in part responsible of cardiac inflammation in T. cruzi infected mice. We also describe the indirect participation of COX-2 in immunosuppression in the acute phase of infection by increasing inducible nitric oxide synthase expression. The key role of lipid mediators in Chagas disease inflammation and the availability of drugs which inhibit their synthesis and their receptors could be useful for the treatment of this neglected disease.