FIG. 1.

Under normal healthy conditions, astrocytes express high levels of TLR9 (generally thought of as antiviral) and low levels of TLR2 (antibacterial). When stimulated through TLR2, cytokine secretion is low, whereas exposure to TLR9 agonists produces a higher secretion of cytokines. When astrocytes are exposed to HIV proteins, including Tat, there is a phenotypic switch, both in vitro and in vivo. This means that if the astrocytes are then stimulated with TLR9 agonists, they fail to produce cytokines, yet when stimulated through TLR2, they produce a cytokine response. This implies that Tat protein hijacks the glia and creates increased activation through TLR2, while limiting the response to HIV viral antigens through TLR9. HIV, human immunodeficiency virus; TLR, Toll-like receptor.