Article
Pivotal Role of Interleukin-12 and Interferon-y Axis in Controlling Tissue Parasitism and Inflammation in the Heart and Central Nervous System during Trypanosoma cruzi Infection
Registro en:
MICHAILOWSKY, Vladimir et al. Pivotal Role of Interleukin-12 and Interferon-y Axis in Controlling Tissue Parasitism and Inflammation in the Heart and Central Nervous System during Trypanosoma cruzi Infection. American Journal of Pathology, v. 159, n. 5, p. 1-11, Nov. 2001.
0002-9440
10.1016/s0002-9440(10)63019-2
1525-2191
Autor
Michailowsky, Vladimir
Silva, Neide M.
Rocha, Carolina D.
Vieira, Leda Q.
Lannes-Vieira, Joseli
Gazzinelli, Ricardo T.
Resumen
The role of cytokines in the control of tissue parasitism
and pathogenesis of experimental Chagas’ disease
was investigated. Wild-type and different cytokine
as well as inducible nitric oxide synthase (iNOS)
knockout mice were infected with the Colombian
strain of Trypanosoma cruzi, and the kinetics of tissue
parasitism, inflammatory reaction, parasitemia,
and mortality were determined. We demonstrate the
pivotal role of the interleukin (IL)-12/interferon
(IFN)- /iNOS axis and the antagonistic effect of IL-4 in
controlling heart tissue parasitism, inflammation,
and host resistance to acute infection with T. cruzi.
Further, the heart and central nervous system were
shown the main sites of reactivation of T. cruzi infection
in mice lacking functional genes for IFN- and
IL-12, respectively. Our results also show that in contrast
to IFN- knockout (KO) mice, splenocytes from
IL-12 KO mice infected with T. cruzi produced low
levels of IFN- upon stimulation with antigen. Consistently,
high levels of anti-T. cruzi IgG2a antibodies
were detected in the sera from IL-12 KO, but not from
IFN- KO mice, infected with the Colombian strain
of T. cruzi. Thus, our results suggest that the level of
IFN- deficiency is a major determinant of the site of
reactivation of T. cruzi infection in immunocompromised
host.