Benznidazole Therapy Modulates Interferon-γ and M2 Muscarinic Receptor Autoantibody Responses in Trypanosoma cruzi-Infected Children

Abstract

ObjectiveThe presence of autoantibodies with adrenergic and cholinergic activity, capable of triggering neurotransmitter receptor-mediated effects, has been associated with pathogenesis in T. cruzi-infected hosts. The goal of this study was to investigate the production of anti-M2 muscarinic receptor autoantibodies (Anti-M2R AAbs) as well as the IFN-γ profile in children at the early stage of Chagas disease, and to examine whether trypanocidal chemotherapy with benznidazole (BZ) could modify both response patterns.MethodsThis study comprised 30 T. cruzi-infected children (mean age: 13.8 years) and 19 uninfected controls (mean age: 12.7 years). Infected patients were treated with BZ and followed-up. Blood samples collected at diagnosis-T0, end of treatment-T1, and six months later-T2 were analysed by ELISA for detection of Anti-M2R AAbs and circulating levels of IFN-γ.ResultsAt T0, anti-M2R AAbs were demonstrated in 56.7% of T. cruzi-infected patients, whereas uninfected controls were 100% negative. The average age of Anti-M2R AAbs+ patients was higher than that from negative population. Infected children also displayed significantly stronger serum IFN-γ responses than controls. Upon BZ treatment, a significant linear decreasing trend in Anti-M2R AAb reactivity was recorded throughout the follow-up, with 29.7–88.1% decrease at T2. IFN-γ circulating levels also declined by T2.ConclusionAnti-M2R AAbs and IFN-γ raise early during chagasic infection in children and are downmodulated by BZ therapy. These findings reinforce the usefulness of early BZ treatment not only to eliminate the parasite but also to reduce potentially pathogenic immune responses.

Simvastatin and Benznidazole-Mediated Prevention of Trypanosoma cruzi-Induced Endothelial Activation: Role of 15-epi-lipoxin A4 in the Action of Simvastatin

“…The reduction in CAM expression and, consequently, cell adhesion was independent of the trypanocidal activity of benznidazole. Indeed, the anti-inflammatory effect of benznidazole had already been reported [ 33 ]. In experimental sepsis models, benznidazole attenuated NF-κB and the MAPK pathway activities, highlighting its immunomodulatory capacity [ 34 , 35 ].…”

Enalapril in Combination with Benznidazole Reduces Cardiac Inflammation and Creatine Kinases in Mice Chronically Infected with Trypanosoma cruzi

“…35 Its immunomodulatory effect goes further through the observation that the benznidazole is able to inhibit inflammatory cytokines, autoantibodies, nitric oxide production, and also leukocyte recruitment into the heart during T. cruzi infection in human and experimental models. [36][37][38][39] In these studies, the toxicity of the benznidazole overrides the cardiac beneficial effects since activation and/or misbalanced of the host inflammatory response become detrimental to the heart function. Yet far from a cure for chronic stage of the infection, a novel therapeutic strategy has been proposed in which immunomodulation in the absence of immunosuppression could be beneficial to the host during chronic T. cruzi infection.…”

Anti-adrenergic and muscarinic receptor autoantibodies in a canine model of Chagas disease and their modulation by benznidazole

“…Since increased fibrosis is a trigger for the development of arrhythmias, our findings are consistent with the effects of Bz treatment in collagen deposition previously reported. Recently, Cutrullis et al [10] reported a significant reduction of serum anti-M 2 -CR titers in children in the indeterminate form of Chagas disease when submitted to Bz treatment, however they could not associate this finding with heart dysfunction as the patients did not show any ECG or ECHO alterations.…”