Experimental autoimmune encephalomyelitis can be prevented and cured by infection with Trypanosoma cruzi.
Trypanosoma cruzi is an intracellular parasite that induces a strong Th1-type response and immunosuppression during the acute phase of infection. To study how the infection with T. cruzi would modulate the development of an autoimmune disease, we immunized C57BL/6 mice and IL-10 or iNOS knock-out mice of the same background with the encephalitogenic MOG 35-55 peptide and infected them with T. cruzi. Our results demonstrate that infection with T. cruzi completely prevents EAE development and furthermore induces complete and lasting remission in mice that were infected with this parasite after they had developed clinical EAE. Nitric oxide and IL-10 participate in triggering the mechanisms associated with EAE suppression by the infection. Decreased lymphoproliferation and increased frequencies of Annexin-positive cells and of T cells bearing CD95, CD95L or CTLA-4 were observed in the spleen from immunized/infected mice, as well as lower IL-2 and increased TGF-beta production in comparison with only immunized mice. Our results indicate that several effector and regulatory mechanisms of the immune response that arise during the acute phase of T. cruzi infection lastingly affect the expansion and/or effector functions of encephalitogenic cells, preventing the onset or inducing complete remission of EAE.
Institute of Biomedical Sciences, Department of Immunology, University of São Paulo, Av. Prof. Lineu Prestes, 1730, ICB/USP - Ed. BIO IV, 05508-900 São Paulo, Brazil.
Carlos E
CE
Tadokoro
Adriana L
AL
Vallochi
Lília S
LS
Rios
Gislâine A
GA
Martins
David
D
Schlesinger
Tainá
T
Mosca
Vijay K
VK
Kuchroo
Luiz V
LV
Rizzo
Ises A
IA
Abrahamsohn
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015551:Autoimmunity; D049109:Cell Proliferation; D014355:Chagas Disease / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000469:parasitology* / Q000517:prevention & control / Q000628:therapy*; D006023:Glycoproteins; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000502:physiology; D052247:Nitric Oxide Synthase Type II; D010446:Peptide Fragments; D012074:Remission Induction / Q000379:methods; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D014349:Trypanosoma cruzi / Q000276:immunology*
D015703:Antigens, CD; D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D016753:Interleukin-10; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse