CD163 identifies a unique population of ramified microglia in HIV encephalitis (HIVE)

Abstract

The idea that CNS ramified microglia are quiescent has been challenged by studies that show that microglia without the classic signs of activation can be phagocytic and appear with shorter, thicker ramifications. These semi-activated cells may constitute a form of microglia that has not been previously recognized in neuropathological conditions and may contribute to the pathology and dysfunction in these disorders. This study investigated the expression of CD163, a cell surface marker whose normal expression is restricted to monocytes/macrophages, in cases of HIV or SIV encephalitis (HIVE/SIVE), Alzheimer disease, and variant Creutzfeldt-Jakob disease. In HIVE/SIVE, in addition to reacting with CNS macrophages, CD163 antibody staining was shown to highlight ramified microglia. Such reactivity was especially notable in grey matter ramified microglia and was greater than that of another typically used marker, HLA-DR. CD163 expression was only observed in infected/affected tissue, in contrast to that shown with another microglia marker, GLUT5, which has recently been shown to identify all microglia regardless of disease state. Although activated microglia were present in the other disorders, as evidenced by strong HLA-DR expression, there was very little CD163 immunoreactivity. The activation state identified by CD163 has not been previously recognized and may have a positive or negative impact on neuronal damage shown in HIV-associated dementia.