Chronic Chagas' Disease Cardiomyopathy Patients Display an Increased IFN-γ Response to Trypanosoma cruzi Infection

Abstract

One-third of all Trypanosoma cruzi -infected patients eventually develop chronic Chagas' disease cardiomyopathy (CCC), a particularly lethal inflammatory dilated cardiomyopathy, where parasites are scarce and heart-infiltrating mononuclear cells seem to be the effectors of tissue damage. Since T. cruzi is a major inducer of interleukin-12 production, the role of inflammatory cytokines in the pathogenesis of CCC was investigated. We assayed cytokine production by peripheral blood mononuclear cells (PBMC) from CCC and asymptomatic T. cruzi -infected (ASY) individuals, as well as by T cell lines from endomyocardial biopsies from CCC patients. PBMC from CCC and ASY patients produced higher IFN-γ levels than normal (N) individuals in response to B13 protein and phytohaemagglutinin PHA; IFN-γ high responders (≥1ng/ml) were 2–3 fold more frequent among CCC patients than ASY individuals. Conversely, IL-4 production in response to the same stimuli was suppressed among T. cruzi -infected patients. The frequency of PHA-induced IFN γproducing cells on PBMC was significantly higher among CCC than ASY and N individuals. IFN-γ and TNF-α were produced by ten out of ten PHAstimulated T cell lines from CCC patients; IL-2 and IL-10 were produced by four out of ten and one out of ten lines, respectively; IL-4, IL-1α, IL-1β, IL-6 and IL-12 were undetectable. Our results suggest that CCC and ASY patients may respond differentially to the IFN-γ-inducing stimulus provided by T. cruzi infection. Given the T1-type cytokine profile of heart-infiltrating T cell lines from CCC patients, the ability to mount a vigorous IFN-γ response may play a role on the differential susceptibility to CCC development.