Phagocytosis of particulate antigens - all roads lead to calcineurin/NFAT signaling pathway

Abstract

Antigen-presenting cells (APC) possess multiple cell surface receptors that recognize common microbe-associated antigens as well as immune complexes and inert particles. Upon encountering such antigens these receptors must cooperate to achieve phagocytosis and trigger signaling cascades that initiate the innate immune response. While the stimuli initiating these signaling cascades are diverse, recent data have revealed that their effects in APC and particularly in dendritic cells (DC), all have something in common: downstream activation of nuclear factor of activated T cells (NFAT). NFAT is a family of transcription factors that has emerged as a key mediator of the initiation of immune responses by APCs, and specifically of IL-2 production by DC as reviewed (1). Intriguingly NFAT activation now seems to be the shared endpoint of several signaling pathways that all begin with uptake of particulate antigens.