Benznidazole affects expression of Th1, Th17 and Treg cytokines during acute experimental Trypanosoma cruzi infection

Abstract

BackgroundThe present study evaluated the effect of treatment with benznidazole on mRNA expression of IFN-γ, IL-17, IL-10, TGF-β and FoxP3 in spleen and heart tissue of BALB/c mice in the acute phase of an experimental infection with Trypanosoma cruzi, strains JLP or Y.MethodsThe mRNA expression of cytokines and parasite load were assessed by q-PCR. Dependent groups were compared using Student’s paired t-test and independent groups were compared using Student’s unpaired t-test.ResultsInfection with the JLP or Y strains increased expression of IFN-γ in the heart and of IL-10 and IL-17 in the spleen and heart compared to uninfected animals. Treatment increased the expression of IFN-γ and decreased the expression of IL-17, IL-10, TGF- β and Foxp3 in spleen and heart tissue compared to untreated infected animals.ConclusionBenznidazole can induce Th1 profile in the initial of the acute phase. The treatment decreased the parasite load in both organs, although the number of parasites in Y-strain-infected mice remained high. The data suggest that benznidazole may modulate cytokine expression in infection and can be dependent of the strain. However, treatment was not fully effective in the infection provoked by Y strain, probably due to the characteristics of the strain itself.

IL-17A, a possible biomarker for the evaluation of treatment response in Trypanosoma cruzi infected children: A 12-months follow-up study in Bolivia

“…However, the ambiguous group (cPCR(-) qPCR(+)) showed a significant decrease of IL-17A after 6 months indicating no persistent infection. This is compatible to the recent report that observed a decrease in the expression of IL-17 in mouse tissue after BNZ [58]. Although we could not make any clear diagnosis on whether the treated is cured or non-cured using serology and PCR, cytokine profile especially IL-17A suggested that parasite infection continued only in the non-reactive group but not in the ambiguous group (Fig 5d).…”

Impact of autologous whole blood administration upon experimental mouse models of acute Trypanosoma cruzi infection

“…We found rises in IFN-gama, TNF-alpha and IL-6 at 9 day after infection in all infected groups as compared to uninfected mice but only Bz displayed statistically significant lower ( p = 0.02) TNF-alpha levels, possibly due to reduced parasitism levels and respective antigenic stimuli. Our cytokine findings corroborate previous studies using murine models of acute infection that reported elevated levels of proinflammatory cytokines IFN-gamma, TNF-alpha, and IL-6 in untreated and infected animals compared to uninfected mice and that Bz reduced the plasmatic levels of these cytokines [ 62 , 63 ]. As to the ponderal curve, only animals treated with Bz after infection showed protection against weight loss, while the other presented a decrease in weight gain.…”

Evaluation of pathogen P21 protein as a potential modulator of the protective immunity induced by Trypanosoma cruzi attenuated parasites

“…As a matter of fact, IFN-γ activation during the acute phase of T. cruzi infection promotes macrophage activation and reactive oxygen species production, and as a consequence, this higher expression leads to the inhibition of parasite replication. 26 Indeed recent studies suggests that IFN-g could avoid tolerogenic circuits and reduce parasite burden in heart and skeletal muscle 27 , 28 and thus favor parasite control in the first steps of infection. Because of these reasons, an up-regulation of IFN-g expression in immunised mice may represent a valuable modulation gained by rP21 supplementation.…”