Intracellular complement in monocytes and macrophages: emerging roles

Macrophages and the complement system are fundamental components of innate immunity, emerging early in evolutionary history. The well-established functions of complement in relation to macrophages contribute to both innate and adaptive immunity and are mediated by extracellular components acting systemically or locally within tissues. A novel compartment, termed intracellular complement or the 'complosome', was first identified in 2013 within CD4+ T cells, marking the onset of an active research field. Intracellular complement has been associated with responses to both infectious and noninfectious stimuli, akin to extracellular complement, while also exhibiting significant autocrine functions in cell metabolism and homeostasis. This review focuses on intracellular complement within monocytes/macrophages. After a brief overview of the complement system and its canonical roles in these cells, we define intracellular complement and discuss current knowledge regarding its expression and functions in monocytes/macrophages, as well as its potential links to human diseases.