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 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.
Aliberti
J C
JC
Departments of Biochemistry and Immunology, School of Medicine of Ribeiräo Preto, University of São Paulo, Ribeiräo Preto, Av Bandeirantes, 3900, 14 049-900, Ribeiräo Preto, São Paulo, Brazil.
Souto
J T
JT
Marino
A P
AP
Lannes-Vieira
J
J
Teixeira
M M
MM
Farber
J
J
Gazzinelli
R T
RT
Silva
J S
JS
D000818:Animals; D015703:Antigens, CD; D002465:Cell Movement; D014355:Chagas Disease / Q000378:metabolism* / Q000473:pathology; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D019743:Chemokines, CXC / Q000378:metabolism; D005260:Female; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000172:deficiency* / Q000502:physiology; D016753:Interleukin-10 / Q000502:physiology; D008214:Lymphocytes / Q000502:physiology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism; D010538:Peritonitis / Q000469:parasitology*; D012333:RNA, Messenger / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency*; D047888:Receptors, Tumor Necrosis Factor, Type I; D016212:Transforming Growth Factor beta / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D015703:Antigens, CD; C111954:CXC chemokine Mig; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D018925:Chemokines; D019743:Chemokines, CXC; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma