Differential susceptibility to acuteTrypanosoma cruziinfection in BALB/c and C57BL/6 mice is not associated with a distinct parasite load but cytokine abnormalities

Abstract

SUMMARY 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‐α on days 14 and 21 p.i., in the presence of lower IL‐1β 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‐α soluble receptors in C57BL/6 mice with no differences in IFN‐γ 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.

A high corticosterone/DHEA-s ratio in young rats infected with Trypanosoma cruzi is associated with increased susceptibility

“…In addition to the immaturity of the immune system described in young rats, our results might be associated with elevated CT values and an elevated CT/DHEA-s ratio, which favours immunosuppression and susceptibility (Figs 3B,4B). These results are in agreement with observations in T. cruzi-infected mice that TNF-α is critical for protection during acute Chagas disease, but could also be deleterious when excessively produced, which would induce vulnerability and death (Roggero et al 2002(Roggero et al , 2004(Roggero et al , 2009. In addition, similar to studies in mice (Roggero et al 2006, Pérez et al 2007), TNF-α production in our infected young rats preceded HPA axis activation and resulted in increased CT levels.…”

Endogenous glucocorticoids cause thymus atrophy but are protective during acute Trypanosoma cruzi infection

“…2. The Balb/c strain is more resistant to infection, since more than half of the animals that received the same number of parasites as the C57Bl/6 mice survive (Roggero et al 2002). In the present study, only 40% of the infected Balb/c mice died within 23$7G0$4 days of infection.…”

“…C thymocytes, while more than 50% of the Balb/c mice recover (Roggero et al 2002). Increased morbidity of C57Bl/6 mice does not seem to result from an aggravated infection since parasitemia, myocardial parasite nests and amastigote counts in peritoneal macrophages were comparable in both strains.…”

“…We have chosen to study, in particular, the significance of endogenous glucocorticoids levels for the course of T. cruzi infection, because the cytokine pattern and the thymic alterations described supported the hypothesis that the hypothalamuspituitary-adrenal (HPA) axis might be activated in the model of Chagas'disease used in our studies. TNF-a, IL-1b, IL-6, and IFN-g, which can stimulate the HPA axis (for review, see Besedovsky & del Rey, 1996, Turnbull & Rivier, 1999, are among the cytokines released during T. cruzi infection (Gao & Pereira, 2002, Roggero et al 2002. Although cytokines produced during infectious diseases can be initially protective, they can also cause tissue injury and metabolic derangements when produced in excess.…”

Triiodothyronine Modulates Thymocyte Migration

“…It should be pointed out that C57BL/6 and BALB/c mouse strains are known to be quite distinct, not only in terms of cytokine profiles [49], but also with respect to their relative susceptibility to hyperthyroidism [50].…”