Macrophage polarization in health and disease

Abstract

Macrophages are terminally differentiated cells of the mononuclear phagocyte system that also encompasses dendritic cells, circulating blood monocytes, and committed myeloid progenitor cells in the bone marrow. Both macrophages and their monocytic precursors can change their functional state in response to microenvironmental cues exhibiting a marked heterogeneity. However, there are still uncertainties regarding distinct expression patterns of surface markers that clearly define macrophage subsets, particularly in the case of human macrophages. In addition to their tissue distribution, macrophages can be functionally polarized into M1 (proinflammatory) and M2 (alternatively activated) as well as regulatory cells in response to both exogenous infections and solid tumors as well as by systems biology approaches.

Keywords: HIV; M1/M2; TAMs (tumor-associated macrophages); macrophage; polarization; regulatory macrophages; tumors.

Figure 1

A model of M1-MDM as “HIV-1-resistant macrophages.” (1) Downmodulation of CD4 and production of CCR5-binding chemokines that compete with gp120 Env for the ligation to the main viral entry coreceptor [23]. (2) Inhibition of viral DNA synthesis and proviral integration [23], (L. Cassetta et al. submitted). (3) Inhibition of proviral transcription (L. Cassetta et al., submitted). (4) Inhibition of HIV-1 protein synthesis [23], (L. Cassetta et al., submitted). (5) Inhibition of new particle assembly and release (hypothetical).