The Alternatively Activated Human—Redux

Abstract

It has long been appreciated that, even in their nonactivated state, tissue-associated macrophages represent a diverse population of cells whose varied functional phenotypes are a product of their local environment. Although derived from the same bone marrow precursors, macrophages that take up residence in the liver, central nervous system, lung, spleen, and adipose tissues adopt distinct functions that are important in maintaining tissue homeostasis and defense against pathogens. Another layer of complexity is revealed when macrophages are activated during innate and adaptive immune responses. It has become clear that activated macrophages, similar to T cells, take on varied activation states that depend on the specific nature of the molecular signals they receive. Building on the initial observations that activated phagocytic cells are a critical component of effective antibacterial immunity [1-3], Nathan et al. [4] demonstrated that lymphocyte-derived interferon-y (IFN-y) is the factor that converts resting macrophages into cells with a markedly enhanced capacity to