Kinetics of cytokine gene expression in experimental chagasic cardiomyopathy: tissue parasitism and endogenous IFN-gamma as important determinants of chemokine mRNA expression during infection with Trypanosoma cruzi.
We investigated the kinetics of parasite replication, leukocyte migration, and cytokine/chemokine mRNA expression in the heart tissue from animals infected with the Colombiana strain of Trypanosoma cruzi. Cardiac tissue parasitism was noticeable at 15 days, peaked around 30 days and was dramatically reduced at 120 days postinfection (p.i.). Kinetic studies showed that the inflammatory infiltrate was dominated by the presence of alphabetaT CD3(+ )CD4(+ )CD8(-), alphabetaT CD3(+ )CD4(-)CD8(+ )lymphocytes and macrophages. The mRNA expression of the monokines IL-1beta and IL-12(p40) was elevated at 15 days p.i. and controlled at later time points. In contrast, TNF-alpha mRNA was expressed throughout the infection. Interestingly, we found that at 15 and 30 days p.i. cytokine expression was dominated by the presence of IFN-gamma mRNA, whereas at 60 days or later time points the balance of type 1 and type 2 cytokines was switched in favor of IL-4 and IL-10 mRNAs. The chemokine mRNAs encoding JE, MIP-1alpha, MIP-1beta, KC, and MIP-2 were all mainly expressed at 15 and/or 30 days p.i. and diminished thereafter. In contrast, the expression of RANTES, MIG and IP-10 mRNAs was augmented at 15 days p.i. and persisted at high levels up to 120 days p.i. Taken together, our results indicate that regulation of IFN-gamma and chemokine expression, associated with decreased tissue parasitism, may be largely responsible for the control of inflammation and immunopathology observed in the cardiac tissue of animals infected with T. cruzi.
Talvani
A
A
Department of Biochemistry and Immunology, ICB, UFMG, Belo Horizonte, Brazil.
Ribeiro
C S
CS
Aliberti
J C
JC
Michailowsky
V
V
Santos
P V
PV
Murta
S M
SM
Romanha
A J
AJ
Almeida
I C
IC
Farber
J
J
Lannes-Vieira
J
J
Silva
J S
JS
Gazzinelli
R T
RT
D000818:Animals; D002478:Cells, Cultured; D002598:Chagas Cardiomyopathy / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D018925:Chemokines / Q000235:genetics*; D019742:Chemokines, CC / Q000235:genetics; D019743:Chemokines, CXC / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006321:Heart / Q000469:parasitology; D007371:Interferon-gamma / Q000235:genetics*; D007700:Kinetics; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology; D018512:Parasitemia; D012333:RNA, Messenger; D014349:Trypanosoma cruzi / Q000276:immunology*
D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; D016207:Cytokines; D012333:RNA, Messenger; D007371:Interferon-gamma