Mast cell-orchestrated immunity to pathogens

Abstract

Although widely associated with various inflammatory diseases, mast cells have an evolutionarily conserved role in host defence and have been shown to make functional contributions to immunity to a broad range of pathogens including bacteria, parasites and possibly viruses. Functioning as sentinels, mast cells quickly recognize pathogens during primary and subsequent infections through various direct and indirect receptors, including Toll-like receptors, receptors for endogenous host by-products of inflammation and Fc receptors, which can bind pathogens through high-affinity antibody-mediated interactions. Mast cells have the potential to be the first responding cell type at a site of infection owing to their ability to degranulate in response to many signs of inflammation and infection and release preformed mediators within seconds of activation. A key function of mast cells during infection is to communicate with many cell types, such as dendritic cells, lymphocytes, neutrophils, macrophages, epithelial cells, endothelial cells and neural cells, both locally at a site of infection and in distant tissues such as lymph nodes. Mast cells act as catalysts for immune responses to pathogens, enhancing the speed and magnitude of both innate and adaptive immune responses, and they can also influence the character of responses by producing unique factors depending on the type of pathogen challenge. These qualities also make them effective targets to enhance immune responses to vaccine antigens. Unique attributes of mast cells, including their abilities to survive after activation, replenish their granules, replicate at sites of inflammation and bind pathogen-specific antibodies after a primary response, highlight their potential to contribute to immunological memory, which may influence host responses to chronic or secondary infections.