Fas ligand-dependent inflammatory regulation in acute myocarditis induced by Trypanosoma cruzi infection.
Fas/Fas ligand (Fas-L) engagement, a potent inducer of apoptosis, is also important for cellular activation, regulation of effector and chemotactic activity, and secretion of chemokines and cytokines. We evaluated the relevance of Fas/Fas-L in the regulation of myocarditis induced by Trypanosoma cruzi infection and observed that in Fas-L(-/-) mice (gld/gld), cardiac infiltration was significantly reduced, accordingly showing less cardiomyocyte destruction. Fluorescence-activated cell sorting analysis of cardiac inflammatory cells showed higher numbers of CD8(+) T cells in BALB/c compared with gld/gld mice but similar levels of lymphocyte function-associated antigen-1, intercellular adhesion molecule, CD2, and CD69 expression; MAC-1(+) myeloid cells and mast cells were increased in BALB/c mice, whereas gld/gld mice exhibited an enrichment of CD4(+/low) T cells. Intracellular labeling of cytokines revealed no clear cardiac skewing of Th1 or Th2 responses, but we found a higher number of interleukin-10(+) cells in gld/gld mice and a deficient expression of vascular cell adhesion molecule-1 on cardiac endothelial cells in gld/gld mice. Finally, we found a population of CD3(+) but CD4/CD8 double negative cardiac T cells in both groups of infected mice, but down-regulation of some adhesion molecules and surface receptors was only observed in gld/gld mice, indicating a targeted T-cell population mostly affected by the lack of Fas-L engagement. These results point to a role for myocarditis regulation by Fas/Fas-L beyond its possible direct relevance in cellular death.
de Oliveira
Gabriel Melo
GM
Fundação Oswaldo Cruz/Instituto Oswaldo Cruz, Departamento de Ultra-estrutura e Biologia Celular (DUBC), Laboratório de Biologia Celular, Rio de Janeiro (RJ); Brazil.
Diniz
Rafaela Lopes
RL
Batista
Wanderson
W
Batista
Marcelo Meuser
MM
Bani Correa
Cristiane
C
de Araújo-Jorge
Tânia Cremonini
TC
Henriques-Pons
Andréa
A
D000208:Acute Disease; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D014355:Chagas Disease / Q000150:complications*; D053222:Fas Ligand Protein / Q000502:physiology*; D007249:Inflammation / Q000209:etiology*; D016753:Interleukin-10 / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D009205:Myocarditis / Q000209:etiology / Q000378:metabolism* / Q000469:parasitology
D053222:Fas Ligand Protein; D016753:Interleukin-10