title: Lack of Galectin-3 Prevents Cardiac Fibrosis and Effective Immune Responses in a Murine Model of Trypanosoma cruzi Infection.
abstract: BACKGROUND
  Chagas disease is caused by the protozoan Trypanosoma cruzi, affecting millions of people worldwide. One of the major causes of mortality in the disease is the cardiomyopathy observed in chronic patients, despite the low number of parasites detected in cardiac tissue. Galectin-3, a carbohydrate-binding protein with affinity for β-galactoside-containing glycoconjugates, is upregulated upon infection, and it has been recently involved in the pathophysiology of heart failure.
  
  
  METHODS
  We investigated the role of galectin-3 in systemic and local responses in a murine model of T. cruzi infection, using knockout animals. Molecular mechanisms underlying galectin-3-dependent inflammatory responses were further assessed in cultured dendritic cells in vitro.
  
  
  RESULTS
  Mice deficient for galectin-3 have elevated blood parasitemia levels and impaired cytokine production during infection. Remarkably, galectin-3 promotes cellular infiltration in the heart of infected mice and subsequent collagen deposition and cardiac fibrosis. Furthermore, we show that an unbalanced Toll-like receptor expression on antigen-presenting cells may be the cause of the impaired immune response observed in galectin-3-deficient mice in vivo.
  
  
  CONCLUSIONS
  These results suggest that galectin-3 is strongly involved in Chagas disease, not only in the immune response against T. cruzi, but also in mediating cardiac tissue damage.
authors: Centro de Biología Molecular Severo Ochoa, Nicolás Cabrera 1, Universidad Autónoma de Madrid, Spain.
authors: Miguel A
authors: MA
authors: Pineda
authors: Centro de Biología Molecular Severo Ochoa, Nicolás Cabrera 1, Universidad Autónoma de Madrid, Spain.
authors: Henar
authors: H
authors: Cuervo
authors: Centro de Biología Molecular Severo Ochoa, Nicolás Cabrera 1, Universidad Autónoma de Madrid, Spain.
authors: Manuel
authors: M
authors: Fresno
authors: Centro de Biología Molecular Severo Ochoa, Nicolás Cabrera 1, Universidad Autónoma de Madrid, Spain.
authors: Manuel
authors: M
authors: Soto
authors: Centro de Biología Molecular Severo Ochoa, Nicolás Cabrera 1, Universidad Autónoma de Madrid, Spain.
authors: Pedro
authors: P
authors: Bonay
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002598:Chagas Cardiomyopathy / Q000276:immunology / Q000517:prevention & control; D014355:Chagas Disease / Q000276:immunology* / Q000469:parasitology; D002522:Chlorocebus aethiops; D005355:Fibrosis / Q000276:immunology / Q000517:prevention & control; D005697:Galactosides / Q000276:immunology; D037502:Galectin 3 / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000276:immunology / Q000473:pathology*; D018512:Parasitemia; D011956:Receptors, Cell Surface / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology*; D014709:Vero Cells
chemical_list: D005697:Galactosides; D037502:Galectin 3; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; C007816:beta-galactoside; C055213:saccharide-binding proteins
keywords: Toll-like receptor; Trypanosoma cruzi; cardiac fibrosis; galectin-3; inflammation; innate immunity