Phenotypic variation in myocardial macrophage populations suggests a role for macrophage activation in SIV-associated cardiac disease.

Cardiac abnormalities are common in HIV-infected individuals, and have been especially well documented as contributors to mortality in HIV-infected children. Underlying pathogenetic mechanisms responsible for myocardial disease in HIV-infection remain imperfectly understood. SIV-infected rhesus monkeys develop a spectrum of cardiac lesions similar to those seen in HIV-infected people, providing an important model for pathogenesis studies. Retrospective analysis of cardiac tissue collected at necropsy from SIV-infected rhesus monkeys was performed to evaluate myocardial macrophage and dendritic cell populations as a function of previously quantitated lymphocytic inflammatory infiltrates and cardiomyocyte degeneration or necrosis. Variations in the size and phenotype of macrophage and dendritic cell populations were examined as possible contributors to the pathogenesis of SIV-associated inflammatory lesions. Macrophages labeling immunohistochemically for CD163 differed substantially from macrophages labeling for HAM56 in overall number, distribution across groups, involvement in inflammatory clusters, correlation with the DC-SIGN(+) subpopulation of macrophages, and correlation with numbers of SIV-infected cells. CD163(+) macrophages occurred in significantly higher numbers in uninflamed hearts from SIV-infected animals than in hearts from SIV-infected animals with myocarditis or uninfected controls (p < 0.01). Numbers of CD163(+) cells correlated positively with numbers of SIV-infected cells (p < 0.05) suggesting that the CD163(+) population was associated with decreased inflammatory infiltration and reduced control of virus within the heart. As CD163 has been associated with nonclassical macrophage activation and an antiinflammatory phenotype, these results suggest that a balance between classical and nonclassical activation may affect levels of inflammatory infiltration and of myocardial virus burden.