title: Granulocyte colony-stimulating factor partially repairs the damage provoked by Trypanosoma cruzi in murine myocardium.
abstract: BACKGROUND
  The hallmark of Trypanosoma cruzi infection is cardiomyopathy that leads to end-stage heart failure. We investigated whether G-CSF, known to induce heart tissue repair by bone marrow stem cell mobilization, ameliorates T. cruzi-induced myocarditis.
  
  
  RESULTS
  T. cruzi-infected C3H/He mice were treated with G-CSF and monitored for parasite burden, BMSC mobilization, cytokine profile and cardiac remodeling. G-CSF increased the expression of CXCR4, CD34, and c-Kit, indicating mobilization and migration of BMSC, some of which differentiated to cardiomyocytes as evidenced by increased levels of GATA4(+)/MEF2C(+) cells and desmin expression in chagasic hearts. G-CSF enhanced a mixed cytokine response (IL-10+TGF-β>IFN-γ+TNF-α>IL-4) associated with increased heart inflammation and no beneficial effect on parasite control. Further, G-CSF controlled T. cruzi-induced extracellular-matrix alterations of collagens (Col I and Col llI), hydroxyproline, and glycosaminoglycan contents and promoted compensatory cardiac remodeling; however, these responses were not sufficient to control T. cruzi-induced cardiomyocyte atrophy. Benznidazole treatment prior to G-CSF resulted in the control of parasitism and parasite-induced inflammation, and subsequently, G-CSF was effective in executing the tissue repair, as evidenced by extracellular-matrix homeostasis and normalization of cardiomyocyte size in chagasic hearts.
  
  
  CONCLUSIONS
  G-CSF treatment after T. cruzi infection enhanced migration and homing of BMSC, some of which differentiated to cardiomyocytes. Yet, G-CSF promoted a mixed (Treg>Th1>Th2) immune response that contributed to persistent inflammation and limited improvement in cardiac homeostasis. Combinatorial therapy (BZ → G-CSF) was beneficial in arresting inflammatory processes and tissue damage in chagasic hearts.
authors.affiliation: Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben", Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Mariela Natacha
authors.initials: MN
authors.lastname: González
authors.forename: Nilay
authors.initials: N
authors.lastname: Dey
authors.forename: Nisha Jain
authors.initials: NJ
authors.lastname: Garg
authors.forename: Miriam
authors.initials: M
authors.lastname: Postan
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002598:Chagas Cardiomyopathy / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D019650:Hematopoietic Stem Cell Mobilization; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D032383:Myocytes, Cardiac / Q000166:cytology; D012074:Remission Induction
chemical_list: D016179:Granulocyte Colony-Stimulating Factor
keywords: Cardiac repair; Chagas disease; G-CSF; Stem cell; Trypanosoma cruzi