Cruzipain, a major Trypanosoma cruzi antigen, conditions the host immune response in favor of parasite.
We recently demonstrated that humoral immune response to cruzipain, a major antigen of Trypanosoma cruzi parasite, is implicated in the pathogenesis of experimental Chagas' disease. In the present study, the spleen cell phenotype and the cytokine profile induced by cruzipain in immunized mice were analyzed. The results showed that cruzipain increases the number of spleen cells with large size and granularity. Splenocyte populations with CD19(+), Mac-1(+), Gr-1(+) and CD11c(+) positive surface markers significantly increased in immune mice compared to controls ones. Histological study revealed the presence of high number of megacariocyte and granulocyte-macrophage progenitors, indicating extramedullary hemopoiesis in spleens of immune mice. The finding of high levels of IL-4, IL5 and IL-10 and low levels of IFN-gamma and IL-12 in supernatants of immune cells stimulated with cruzipain indicates a preferential activation of T2 type cells in immune animals. To investigate the role of innate immunity cells, the classical and alternative metabolic pathways of spleen macrophages from immune mice stimulated by cruzipain were also studied. The results showed an increase of urea associated with a decrease of nitrite levels, suggesting that cruzipain up-regulates the arginase way. Therefore, cruzipain leads to T2 type cytokine profile which may enhance the arginase via in the macrophages promoting a susceptible mechanism to infection. Thus, we postulate that during T. cruzi infection, cruzipain could be used by the parasite to spread inside the host.
Giordanengo
Laura
L
Inmunología, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Guiñazú
Natalia
N
Stempin
Cinthia
C
Fretes
Ricardo
R
Cerbán
Fabio
F
Gea
Susana
S
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D001119:Arginase / Q000502:physiology; D014355:Chagas Disease / Q000276:immunology*; D003546:Cysteine Endopeptidases / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004198:Disease Susceptibility; D005260:Female; D006411:Hematopoiesis, Extramedullary; D006790:Host-Parasite Interactions; D008262:Macrophage Activation; D008264:Macrophages / Q000201:enzymology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013163:Splenomegaly / Q000209:etiology / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology*
D000953:Antigens, Protozoan; D016207:Cytokines; D015800:Protozoan Proteins; D003546:Cysteine Endopeptidases; C063214:cruzipain; D001119:Arginase