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(American Journal of Pathology. 2001;158:1433-1440.)
© 2001 American Society for Investigative Pathology

Regular Articles

Modulation of Chemokine Production and Inflammatory Responses in Interferon-- and Tumor Necrosis Factor-R1-Deficient Mice during Trypanosoma cruzi Infection

Júlio C. S. Aliberti^*, Janeusa T. Souto^*, Ana P. M. P. Marino, Joseli Lannes-Vieira, Mauro M. Teixeira, Joshua Farber^§, Ricardo T. Gazzinelli and João S. Silva^*

From the Departments of Biochemistry and Immunology,^*
School of Medicine of Ribeiräo Preto, University of São Paulo, Ribeiräo Preto, São Paulo, Brazil; the Federal University of Minas Gerais,
Belo Horizonte, Brazil; the Department of Immunology, Fundação Osvaldo Cruz,
Rio de Janeiro, Brazil; and the Laboratory of Clinical Investigation,^§
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland

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. cruzi-induced chemokine expression in vivo and in vitro. In macrophage cultures, although the stimulation with interferon (IFN)- increases the expression of IP-10, it blocks KC expression. Tumor necrosis factor (TNF)-, on the other hand, potentiates KC, IP-10, macrophage inflammatory protein-1, and JE/monocyte chemotatic protein-1 expression. Interleukin-10 and transforming growth factor-ß inhibited almost all chemokines tested. The role of IFN- and TNF- in chemokine modulation during infection was investigated in T. cruzi-infected IFN--deficient (GKO) or TNF-R1/p55-deficient (p55-/-) 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 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. Together, these results suggest that the regulatory roles of IFN- and TNF- on chemokine expression may play a crucial role in the modulation of the inflammatory response during T. cruzi infection and mediate resistance to infection.

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