Macrophages are a type of white blood cell that engulfs and digests cellular debris, foreign substances, microbes, cancer cells, and anything else that is not recognised as part of the host. This process is called phagocytosis. Besides phagocytosis, they play a critical role in innate immunity and also help initiate specific defence mechanisms (adaptive immunity) by recruiting other immune cells such as lymphocytes. They are important as antigen presenters to T cells, linking the innate and adaptive immune systems.
Beyond increasing inflammation and stimulating the immune system, macrophages also play an important anti-inflammatory role and can decrease immune reactions through the release of cytokines. Macrophages that encourage inflammation are called M1 macrophages, whereas those that decrease inflammation and encourage tissue repair are called M2 macrophages.
Distinct subpopulations of macrophages can be defined by their tissue of residence and functional phenotype. Each of these macrophage populations can be identified based on their expression or lack of expression of specific cell surface receptors and intracellular markers. Due to local stimuli in their environments or specialized functions associated with their tissue of residence, tissue-resident macrophages frequently express specific transcription factors that direct their activities. Macrophages also display great flexibility and plasticity depending on signals in their environments. As a result, their markers can be altered by external stimuli that modify their transcriptional programs and lead to an activated state.
Tissue-resident macrophages are a heterogeneous group of cells that express a variety of cell surface and intracellular markers. Although their markers frequently differ based on their anatomical locations and functions, there is some overlap in the markers that are expressed on different macrophage subpopulations. Some common receptors expressed on multiple mouse macrophage subpopulations include CD115/M-CSF R, F4/80, CD11b/Integrin alpha M, CD68, CD163, and Fc receptors. There are also a number of receptors that have been implicated in phagocytosis or ligand recognition that are frequently expressed by macrophages including scavenger receptors, toll-like receptors (TLRs), Nod-like receptors (NLRs), and some C-type lectin receptors.
Following development, macrophages encounter diverse stimuli, which can alter their transcriptional programs leading to an activated state. The classic view of macrophage activation is described in a dichotomous model. According to this model, classical (M1) macrophage activation is induced by IFN-gamma or lipopolysaccharide (LPS) and promotes a pro-inflammatory response, while alternative (M2) macrophage activation is induced by IL-4, IL-10, or IL-13 and stimulates an anti-inflammatory response. Slight phenotypic variations noted in the M2 phenotype led to the description of different M2 subsets known as M2a, M2b, M2c, M2d, which were defined based on the stimuli used for activation. It has been widely recognized however, that even this expanded model of macrophage activation is too simple to account for the range of phenotypes observed in macrophages under different conditions. For this reason, a new multidimensional model of macrophage activation has been proposed. This model suggests that a spectrum of activation states spanning the M1/M2 states can occur in response to diverse signals including ontogeny-related signals, tissue-specific signals, and stress signals, which are integrated to determine the macrophage response.
Click on the images below to find out more about other immune cell types.