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

Am J Pathol. 2001 Apr;158(4):1433-40. doi: 10.1016/s0002-9440(10)64094-1.


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)-gamma increases the expression of IP-10, it blocks KC expression. Tumor necrosis factor (TNF)-alpha, on the other hand, potentiates KC, IP-10, macrophage inflammatory protein-1alpha, and JE/monocyte chemotatic protein-1 expression. Interleukin-10 and transforming growth factor-beta inhibited almost all chemokines tested. The role of IFN-gamma and 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 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-gamma and TNF-alpha on chemokine expression may play a crucial role in the modulation of the inflammatory response during T. cruzi infection and mediate resistance to infection.

MeSH terms

  • Animals
  • Antigens, CD
  • Cell Movement
  • Chagas Disease / metabolism*
  • Chagas Disease / pathology
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Chemokines / biosynthesis*
  • Chemokines / genetics
  • Chemokines, CXC / metabolism
  • Female
  • Immunophenotyping
  • Interferon-gamma / deficiency*
  • Interferon-gamma / physiology
  • Interleukin-10 / physiology
  • Lymphocytes / physiology
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Myocardium / metabolism
  • Peritonitis / parasitology*
  • RNA, Messenger / metabolism
  • Receptors, Tumor Necrosis Factor / deficiency*
  • Receptors, Tumor Necrosis Factor, Type I
  • Transforming Growth Factor beta / physiology
  • Tumor Necrosis Factor-alpha / physiology


  • Antigens, CD
  • CXC chemokine Mig
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Chemokines
  • Chemokines, CXC
  • RNA, Messenger
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma