Essential role of VLA-4/VCAM-1 pathway in the establishment of CD8+ T-cell-mediated Trypanosoma cruzi-elicited meningoencephalitis.
Central nervous system (CNS) damage can occur during Trypanosoma cruzi infection, especially in immunosuppressed patients. The enhanced susceptibility of C3H/He mice to CD8-mediated acute meningoencephalitis is associated with higher up-regulation of vascular cell adhesion molecule-1 (VCAM-1) on CNS vascular endothelia than in the less susceptible C57BL/6. Further, in vitro adhesion of activated peripheral blood cells to CNS blood vessels was abrogated by anti-VLA-4 antibodies that also inhibited cell migration into the CNS of T. cruzi-infected mice. Lastly, the reactivation of meningoencephalitis in immunosuppressed chronically infected mice was associated with VCAM-1 up-regulation. Therefore, we hypothesize that VLA-4/VCAM-1 pathway plays a pivotal role in the establishment of T. cruzi-elicited encephalitis.
D000818:Animals; D000953:Antigens, Protozoan / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000469:parasitology; D002448:Cell Adhesion / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D020808:Central Nervous System Protozoal Infections / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D014355:Chagas Disease / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D039041:Integrin alpha4beta1 / Q000096:biosynthesis / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000276:immunology / Q000469:parasitology; D008590:Meningoencephalitis / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012008:Recurrence; D015398:Signal Transduction / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000502:physiology*
D000953:Antigens, Protozoan; D007166:Immunosuppressive Agents; D039041:Integrin alpha4beta1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1