Differential susceptibility to acute Trypanosoma cruzi infection in BALB/c and C57BL/6 mice is not associated with a distinct parasite load but cytokine abnormalities.
Inoculation of Trypanosoma cruzi, Tulahuén strain, into C57BL/6 and BALB/c mice led to an acute infection characterized by marked parasitaemia, myocardial inflammation and thymocyte depletion. While C57BL/6 mice showed a progressive and lethal disease, BALB/c mice partly recovered. To characterize these murine models more effectively, we studied the parasite burden, serum levels of major infection outcome-related cytokines, the in vitro features of T. cruzi infection in peritoneal macrophages and the immunophenotype of thymic cells. The greater disease severity of T. cruzi-infected C57BL/6 mice was not linked to an increased parasite load, as parasitaemia, myocardial parasite nests and amastigote counts in peritoneal macrophages were not different from those in BALB/c mice. Cortical thymocyte loss was accompanied by the presence of apoptotic bodies and fragmented nuclear DNA, whereas fluorocytometric analysis at 17 days postinfection (p.i.) revealed a more pronounced loss of CD4+ CD8+ cells in C57BL/6 mice. This group displayed higher levels of TNF-alpha on days 14 and 21 p.i., in the presence of lower IL-1beta and IL-10 concentrations by days 14 and 21, and days 7 and 14 p.i., respectively. Day-21 evaluation showed higher concentrations of nitrate and TNF-alpha soluble receptors in C57BL/6 mice with no differences in IFN-gamma levels, with respect to the BALB/c group. Increased morbidity of C57BL/6 T. cruzi-infected mice does not seem to result from an aggravated infection but from an unbalanced relationship between pro- and anti-inflammatory mediators.
Roggero
E
E
Instituto de Inmunologia, Facultad de Ciencias Médicas de Rosario, Argentina.
Perez
A
A
Tamae-Kakazu
M
M
Piazzon
I
I
Nepomnaschy
I
I
Wietzerbin
J
J
Serra
E
E
Revelli
S
S
Bottasso
O
O
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000469:parasitology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000469:parasitology; D002478:Cells, Cultured; D002598:Chagas Cardiomyopathy / Q000276:immunology* / Q000401:mortality / Q000469:parasitology / Q000503:physiopathology; D014355:Chagas Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D016207:Cytokines / Q000276:immunology*; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000276:immunology; D018512:Parasitemia / Q000276:immunology / Q000469:parasitology; D013045:Species Specificity; D013950:Thymus Gland / Q000166:cytology; D013997:Time Factors; D014349:Trypanosoma cruzi / Q000276:immunology; D015431:Weight Loss
D016207:Cytokines; D008070:Lipopolysaccharides; D009569:Nitric Oxide