Considering the efficacy of
rapamycin in increasing lifespan and healthspan, attenuating the aging-dependent immunological decline, we compared the evolution of
Trypanosoma cruzi infection and acute
myocarditis in young and elderly mice untreated and chronically treated with this
drug. Five groups were investigated: young uninfected and infected, elderly uninfected and infected with Trypanosoma cruzi untreated and treated with
rapamycin (4 mg/kg every 3 days) from the 8th to the 96th week of age. Seven days after the last treatment, elderly mice were inoculated with T. cruzi. Young animals were infected at 8-weeks-old. Untreated elderly mice exhibited increase
parasitemia, parasite load and
myocarditis, which were associated to down-regulation in
IL-2,
IL-6, IFN-γ, TNF,
anti-T. cruzi
immunoglobulin G (
IgG) total,
IgG1 and
IgG2a plasma levels,
inducible nitric oxide synthase (iNOS) gene expression and
nitric oxide (NO) cardiac production, as well as upregulation in Arginase-1 gene expression and
arginase activity compared to young animals. These parameters were improved in
rapamycin-pretreated elderly mice, which exhibited a better parasitological control, reduced heart
inflammation and microstructural damage. These responses were associated with a better balance between Th1 and Th2 effectors similar to that observed in young animals, including an improved activation of Th1
cytokines and the iNOS pathway that positively regulates NO biosynthesis, contradicting the predominant activation of the
arginase pathway in untreated elderly animals. Thus, our findings suggest that chronic pretreatment with
rapamycin can attenuate immunosenescence in mice, contributing to prolong parasite resistance and attenuate acute
myocarditis in elderly host challenged by T. cruzi.