Analysis of interferon-gamma-dependent and -independent pathways of macrophage activation.

Macrophages are a cellular cornerstone of the innate immune response. The outcome of macrophage activity during development of an immune response to microbes results from macrophage activation by both organism-derived and host-derived factors. In order to more fully understand the spectrum of responses expressed by macrophages when encountering these distinct stimuli, we investigated the similarities and differences between interferon-gamma receptor (IFN-gammaR)-dependent macrophage activation and stimulation of macrophages through the Type A1 scavenger receptor (SR). We observed distinct patterns of macrophage activation depending on the nature of the ligand. IFN-gamma and the SR ligand lipotechoic acid (LTA) induced largely non-overlapping sets of genes. The use of two additional SR ligands, maleylated bovine serum albumin and the polydeoxynucleotide poly dI:dC, revealed differences within SR activation-induced gene expression. We also observed that priming with IFN-gamma resulted in an enhanced response to subsequent SR-mediated activation. These results suggest that full potentiation of macrophage activity during development of an antimicrobial immune response is achieved by activation of these cells through multiple receptors.