Article
Modulation of Chemokine Production and Inflammatory Responses in Interferon-g- and Tumor Necrosis Factor-R1-Deficient Mice during Trypanosoma cruzi Infection
Registro en:
ALBERTI, Júlio C. S. et al. Modulation of Chemokine Production and Inflammatory Responses in Interferon-g- and Tumor Necrosis Factor-R1-Deficient Mice during Trypanosoma cruzi Infection. American Journal of Pathology, v. 158, n. 4, p. 1-8, Apr. 2001.
0002-9440
10.1016/s0002-9440(10)64094-1
1525-2191
Autor
Aliberti, Júlio C. S.
Souto, Janeusa T.
Marino, Ana P. M. P.
Lannes-Vieira, Joseli
Teixeira, Mauro M.
Farber, Joshua
Gazzinelli, Ricardo T.
Silva, João S.
Resumen
Infection with Trypanosoma cruzi causes a strong
inflammatory reaction at the inoculation site and,
later, in the myocardium. The present study investigates
the role of cytokines as modulators of T. cruziinduced
chemokine expression in vivo and in vitro. In
macrophage cultures, although the stimulation with
interferon (IFN)-g increases the expression of IP-10,
it blocks KC expression. Tumor necrosis factor
(TNF)-a, on the other hand, potentiates KC, IP-10,
macrophage inflammatory protein-1a, and JE/monocyte
chemotatic protein-1 expression. Interleukin-10
and transforming growth factor-b inhibited almost all
chemokines tested. The role of IFN-g and TNF-a in
chemokine modulation during infection was investigated
in T. cruzi-infected IFN-g-deficient (GKO) or TNFR1/
p55-deficient (p552/2) mice. The expression of
chemokines detected in the inoculation site correlated
with the infiltrating cell type observed. Although
GKO mice had a delayed and intense neutrophilic
infiltrate correlating with the expression of KC and
macrophage inflammatory protein-2, none of the
above was observed in p552/2 mice. The detection of
infiltrating T cells, Mig, and IP-10 in the myocardium
was observed in wild-type and p552/2, but not in
GKO mice. Together, these results suggest that the
regulatory roles of IFN-g and TNF-a on chemokine
expression may play a crucial role in the modulation
of the inflammatory response during T. cruzi infection
and mediate resistance to infection.