Timing of Expression of Inflammatory Mediators in Skeletal Muscles from Mice Acutely Infected with the RA Strain of <i>Trypanosoma cruzi</i>

Abstract

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-γ, TNF-α 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.

Elevated Serum Levels of Macrophage Migration Inhibitory Factor Are Associated with Progressive Chronic Cardiomyopathy in Patients with Chagas Disease

“…We herein found that chronically infected mice display progressive MIF overexpression in cardiac myocytes which is likely to contribute to parasite-triggered inflammatory cardiomyopathy. Previous reports have revealed that the myocardium is itself a significant source of MIF [47], [50] and the expression of this cytokine in cardiomyocytes is upregulated upon heart injury [51].…”

Inflammatory changes in the central nervous system are associated with behavioral impairment in Plasmodium berghei (strain ANKA)-infected mice

“…in the serum (Figure 6), predicting the large increase in infiltrating leukocytes in the brain microvasculature (Figures 3 and 5) and the onset of functional deficits (Figure 2). This CXCR3 ligand is associated with macrophage activation (Menke et al, 2008) and leukocyte infiltration in a number of inflammatory disease states associated with parasite infection, including Chagas disease (Cutrullis et al, 2009). Whether CXCL9 in our model was produced by neural cells or by an early wave of infiltrating macrophages and whether the brain CXCL9 promoted additional macrophage recruitment and/or T cell recruitment remains to be determined.…”

Trypanosoma cruzi Infection and Endothelin-1 Cooperatively Activate Pathogenic Inflammatory Pathways in Cardiomyocytes

“…The sections were analyzed in a Leica DMD 108 microscope (Leica Microsystems, Germany). For immunohistochemical studies, myocardial sections were deparaffinized by routine procedures and analyzed using anti-murine COX-2 rabbit polyclonal antibody (Abcam) and biotinylated swine antiserum to rabbit immunoglobulin (Dako), following a procedure previously described [33].…”