Intercellular adhesion molecule 1 deficiency leads to impaired recruitment of T lymphocytes and enhanced host susceptibility to infection with Trypanosoma cruzi.
In this study, we investigated the involvement of Th1 cytokines in the expression of cell adhesion molecules (CAM) and recruitment of inflammatory cells to the heart of mice infected with Trypanosoma cruzi. Our results show that endogenously produced IFN-gamma is essential to induce optimal expression of VCAM-1 and ICAM-1 on the cardiac vascular endothelium of infected mice. Furthermore, the influx of inflammatory cells into the cardiac tissue was impaired in Th1 cytokine-deficient infected mice, paralleling the intensity of VCAM-1 and ICAM-1 expression on the vascular endothelium. Consistent with the importance of ICAM-1 in host resistance, ICAM-1 knockout (KO) mice were highly susceptible to T. cruzi infection, as assessed by mortality rate, parasitemia, and heart tissue parasitism. The enhanced parasitism was associated with a decrease in the numbers of CD4(+) and CD8(+) T lymphocytes in the heart tissue of ICAM-1 KO mice. Additionally, ICAM-1 KO mice mounted an unimpaired IFN-gamma response and IFN-gamma-dependent production of reactive nitrogen intermediates and parasite- specific IgG2a. Supporting the participation of ICAM-1 in cell migration during T. cruzi infection, the entrance of adoptively transferred PBL from T. cruzi-infected wild-type C57BL/6 mice into the cardiac tissue of ICAM-1 KO mice was significantly abrogated. Therefore, we favor the hypothesis that ICAM-1 plays a crucial role in T lymphocyte recruitment to the cardiac tissue and host susceptibility during T. cruzi infection.
Michailowsky
Vladimir
V
Laboratory of Immunopathology, Centro de Pesquisas Rene Rachou-Fundaçao Oswaldo Cruz, Belo Horizonte, Brazil.
Celes
Mara R N
MR
Marino
Ana P
AP
Silva
Andréa A
AA
Vieira
Leda Q
LQ
Rossi
Marcos A
MA
Gazzinelli
Ricardo T
RT
Lannes-Vieira
Joseli
J
Silva
João S
JS
D000818:Animals; D002465:Cell Movement; D014355:Chagas Disease / Q000276:immunology*; D004198:Disease Susceptibility; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D018664:Interleukin-12; D007371:Interferon-gamma