Infection-associated vasculopathy in experimental chagas disease pathogenic roles of endothelin and kinin pathways.

摘要: Abstract Acting at the interface between microcirculation and immunity, Trypanosoma cruzi induces modifications in peripheral tissues which translate into mutual benefits to host/parasite balance. In this chapter, we will review evidence linking infection-associated vasculopathy proinflammatory activity of a small subset T. molecules, namely GPI-linked mucins, cysteine proteases (cruzipain), surface glycoproteins trans -sialidase family and/or parasite-derived eicosanoids (thromboxane A 2 ). Initial insight pathogenesis came from research animal models showing that myocardial fibrosis is worsened as result endothelin upregulation by infected cardiovascular cells. Paralleling these studies, kinin system emerged proteolytic mechanism links oedematogenic inflammation immunity. Analyses dynamics revealed tissue culture trypomastigotes elicit interstitial oedema sites infection through synergistic activation toll-like receptors (TLR2) G-protein-coupled bradykinin receptors, respectively, engaged tGPI (TLR2 ligand) peptides (bradykinin B2 (BK R) ligands) proteolytically generated cruzipain. Further downstream, kinins stimulate lymph node dendritic cells via BK R, thus converting specialized antigen-presenting T H 1 inducers. Tightly regulated angiotensin-converting enzyme, intact R agonists) may be processed carboxypeptidase M/N, generating [des-Arg]-kinins, activates subtype GPCR upregulated during inflammation. Ongoing studies clarify if discrepancies phenotypes strains ascribed, least part, variable expression TLR2 ligands cruzipain isoforms.