IL-27 regulation of innate immunity and control of microbial growth

Abstract

IL-27 is a pleiotropic cytokine capable of influencing both innate and adaptive immune responses. With anti- and pro-inflammatory activity, IL-27 exerts its opposing effects in a cell-dependent and infectious context-specific manner. Upon pathogenic stimuli, IL-27 regulates innate immune cells, such as monocytes, dendritic cells, macrophages and neutrophils. Immune responses involving these innate cells that are negatively regulated by IL-27 signaling include inflammatory cytokine production, phagolysosomal acidification following phagocytosis, oxidative burst and autophagy. IL-27 signaling is crucial in maintaining the subtle balance between Th1 and Th2 immunity, in which protective inflammation is upregulated within the early stages of infection and subsequently downregulated once microbial growth is controlled. The immunomodulatory effects of IL-27 provide promising therapeutic targets for multiple disease types. Lay abstract A primary role of IL-27 is to communicate between various immune cells to initiate different immune responses. Among these responses are those involved with destroying and eliminating microbial pathogens and then turning off inflammatory responses when the infectious threat has been resolved. IL-27 possesses both anti- and pro-inflammatory activity that varies with context, immune cell and pathogen stimulus. Depending on the precise formula of these details, there are important implications for IL-27 in disease outcomes. As such, harnessing or opposing IL-27 activity may have the potential to treat a variety of infectious diseases.