Alternative activation of macrophages

Abstract

Macrophages are a heterogeneous population of resident and recruited cells that are found in all organs and are involved in tissue homeostasis and defence of the host. The cells express a wide range of surface receptors, which mediate their recognition of endogenous and microbial ligands. Activation of macrophages by surface ligands and cytokines induces a spectrum of pro- and anti-inflammatory states, which are responsible for immune activation and deactivation. The T helper 2 (T_H2) cytokines interleukin-4 (IL-4) and IL-13 induce a characteristic, stereotypical, 'alternative' activation state of macrophages that is distinct from the 'classical' T_H1-type activation by interferon-γ and deactivation by IL-10 and transforming growth factor-β. The effects of IL-4 and IL-13 on macrophages contribute to clearance, presentation of antigens and repair in allergic immune reactions and parasite-induced granuloma formation. Useful markers of alternative macrophage activation include induction of expression of the mannose receptor, MHC class II molecules and selected chemokines, as well as new gene products that have been discovered by gene-expression studies. In this review, I argue for a more limited definition of alternative activation by IL-4 and IL-13, which act through a common receptor subunit, and I distinguish this form of activation from other forms of immunomodulation. This model lends itself to further study of macrophages by gene profiling and proteomics, and it might become extended to a range of other forms of modified immune responses, with potential therapeutic benefits.