Trypanosoma cruzi infection induces the expression of CD40 in murine cardiomyocytes favoring CD40 ligation-dependent production of cardiopathogenic IL-6.

The inflammatory response in the myocardium is an important aspect of the pathogenesis of Chagas' heart disease raised by Trypanosoma cruzi. CD40, a transmembrane type I receptor belonging to the tumor necrosis factor receptor (TNFR) family, is expressed in a broad spectrum of cell types and is crucial in several inflammatory and autoimmune diseases. Activation of CD40 through ligation to CD40L (CD154) induces multiple effects, including the secretion of proinflammatory molecules. In the present study, we examined the ability of T. cruzi to trigger the expression of CD40 in cardiac myocytes in vitro and in a murine model of chagasic cardiomyopathy. Our results indicate, for the first time, that T. cruzi is able to induce the expression of CD40 in HL-1 murine cardiomyocytes. Moreover, ligation of CD40 receptor upregulated interleukin-6 (IL-6), associated with inflammation. Furthermore, the induction of this costimulatory molecule was demonstrated in vivo in myocardium of mice infected with T. cruzi. This suggests that CD40-bearing cardiac muscle cells could interact with CD40L-expressing lymphocytes infiltrating the heart, thus contributing to inflammatory injury in chagasic cardiomyopathy.

Timing of expression of inflammatory mediators in skeletal muscles from mice acutely infected with the RA strain of Trypanosoma cruzi.

OBJECTIVE: Chagas' disease is caused by persistent Trypanosoma cruzi infection in muscle cells that ultimately results in chronic inflammation and tissue destruction. The goal of this study was to determine the expression of different chemokines and their receptors, as well as proinflammatory cytokines and inducible nitric oxide synthase, in muscles from mice acutely infected with T. cruzi. METHODS: Histological, semiquantitative reverse transcriptase polymerase chain reaction and immunohistochemical studies were performed on skeletal muscle and myocardium of BALB/c mice infected with T. cruzi, RA strain. RESULTS: Early induction of muscular mRNA expression for CCL5/CCR5 and CXCL9/CXCR3, as well as for iNOS, IFN-gamma, TNF-alpha and MIF, was demonstrated accompanied by progressive increases in parasitism and leukocyte recruitment. Protein overexpression for MIF and CCL5/CCR5 was also verified in the infected muscles. CONCLUSIONS: In muscles from acutely T. cruzi RA-infected mice, upregulated gene expression of proinflammatory chemokines, chemokine receptors, cytokines and iNOS is associated with the severity of parasite burden and myopathic alterations. Compared to the heart, striated muscles displayed differential timing of expression of several inflammatory mediators throughout acute infection. Our findings suggest that enhanced early production of these factors could contribute to T. cruzi-dependent inflammatory damage to skeletal muscles.