Control of iron homeostasis as a key component of macrophage polarization

In response to microenvironmental signals, innate recognition of tissue damage or pathogen exposure, and signals from activated lymphocyte subsets, macrophages undergo adaptive responses essential for a coordinated immune response, resistance to pathogens, and tissue repair. During the last few years increasing evidence has accumulated indicating that macrophage plasticity can be viewed as a spec trum of activation status between the classic pro-inflammato ry (M1) program, induced by bacterial moieties such as lipopolysaccharides and the Th1 cytokine interferon- γ, and the alternative tissue repair-prone (M2) program, originally discovered as a response to the Th2 cytokine interleukin-4, mirroring Th1/Th2 polarization. 1 It is now appreciated that M2-like functional phenotypes can also be induced by other signals, including antibody immune complexes together with lipopolysaccharides/interleukin-1, glucocorticoids, transform ing growth factor beta- β, and interleukin-10. 2