Analysis of classical and alternative activation in heart tissue during acute Trypanosoma cruzi infection in mice: arginase I is expressed in infiltrating CD68+ macrophages.

CUERVO H; PINEDA MA; AOKI MP; GEA S; FRESNO M; GÌRONÉS N

JOURNAL OF INFECTIOUS DISEASES

Año: 2007

0022-1899

In Chagas’ disease, caused by Trypanosoma cruzi, macrophages, cardiac and skeletal muscle cells are the main targets of infection. Parasite replication is controlled by Th1 responses and classical activation of macrophages, and linked to immune suppression. Contrarily, Th2 responses and alternative activated macrophages are thought to favour host cell growth and T. cruzi survival in vitro. We studied the expression of inducible nitric oxide synthase and arginase, as markers of classical and alternative activation, respectively, in heart tissue during in vivo infection of susceptible BALB/c and resistant C57BL/6 mice. We found that expression of both enzymes, as well as ornithine decarboxylase, was higher in heart tissue of susceptible mice in comparison with resistant mice, and induced with kinetics related to parasite burden in the heart. In addition, inducible nitric oxide synthase and arginase II expression were localized in cardiomyocytes. In contrast, we identified, by confocal microscopy that heart infiltrated CD68+ macrophages were the major cell type expressing arginase I during in vivo T. cruzi infection in both strains. In vitro T. cruzi infection of macrophages and cardiomyocytes did not induce arginase I, suggesting that its expression in vivo is cytokine dependent. Although both Th1 and Th2 cytokines were expressed in heart tissue in both infected mice strains, the Th1/Th2 balance was skewed to Th1 in C57BL/6 mice and to Th2 in BALB/c mice at the peak of parasite infection. Our results demonstrate the expression of arginase I in heart infiltrating CD68+ macrophages that could influence host and parasite cell survival, but might be also down-regulating the counter productive effects of vasodilation, contractility, cardiac pathology and immune suppression triggered by inducible nitric oxide synthase during disease.