Macrophages are sentinel cells of the innate immune response. Macrophages recognise pathogen-associated molecular patterns (e.g. microbial products) and endogenous ligands (e.g. apoptotic cells) through a broad and adaptable range of pattern-recognition receptors. The consequence of this recognition is generally effective clearance via phagocytosis; however, when this is not effective, macrophages may become inappropriately activated and initiate an inappropriate inflammatory response. Because macrophages are extremely variable in phenotype and function and share a common ancestry with monocytes and dendritic cells, there are very few genes that are expressed exclusively in macrophages. Consequently, macrophage-specific immunodeficiencies are rare. There are, however, a number of genetic immunodeficiencies that affect macrophage function. In addition, as macrophages are exquisitely attuned to their microenvironment, their function appears to be adversely affected by and contributes to chronic inflammatory conditions such as cancer, atherosclerosis and obesity. Thus, genetic deficiencies, in addition to microenvironmental dysregulation, can contribute to macrophage function disorders. Key Concepts: Key Concepts: * Macrophages functions include sensing of modified host proteins, microbes and microbial components. Macrophages respond to these ligands primarily through phagocytic and inflammatory receptors. * Macrophage function is exquisitely attuned to the microenvironment and when chronic inflammatory conditions alter the microenvironment, macrophage function can become impaired. * Primary immunodeficiencies have been identified that impair macrophage phagocytosis and inflammatory responses and leave the patient susceptible to infectious disease and other chronic conditions. * Macrophages are able to sense a wide and diverse variety of endogenous and exogenous ligands, including modified host proteins, microbes, and microbial components. * Chronic inflammatory conditions such as cancer and atherosclerosis alter the microenvironment, which can impair the ability of macrophages to maintain homeostasis.
