Modulation of chemokine production and inflammatory responses in interferon-gamma- and tumor necrosis factor-R1-deficient mice during Trypanosoma cruzi infection

Infection with Trypanosoma cruzi causes a strong inflammatory reaction at t he inoculation site and, later, in the myocardium, The present study invest igates the role of cytokines as modulators of T. cruzi-induced chemokine ex pression in vivo and in vitro, In macrophage cultures, although the stimula tion with interferon (IFN)-gamma increases the expression of IP-10, it bloc ks KC expression, Tumor necrosis factor (TNF)-alpha, on the other hand, pot entiates KC, IP-10, macrophage inflammatory protein-1 alpha, and JE/monocyt e chemotatic protein-1 expression. Interleukin-10 and transforming growth f actor-beta inhibited almost all chemokines tested. The role of IFN-gamma an d TNF-alpha in chemokine modulation during infection was investigated in T, cruzi-infected IFN-gamma -deficient (GKO) or TNF-R1/p55-deficient (p55-/-) mice. The expression of chemokines detected in the inoculation site correl ated with the infiltrating cell type observed. Although GKO mice had a dela yed and intense neutrophilic infiltrate correlating with the expression of KC and macrophage inflammatory protein-2, none of the above was observed in p55-/- mice, The detection of infiltrating T cells, Mig, and IP-10 in the myocardium was observed in wild-type and p55-/-, but not in GKO mice. Toget her, these results suggest that the regulatory roles of IFN-gamma and TNF-a lpha on chemokine expression may play a crucial role in the modulation of t he inflammatory response during T, cruzi infection and mediate resistance t o infection.