Emerging Roles of an innate immune regulator tape in the toll-like receptor and RIG-I-like receptor pathways

Inflammation alerts the mammalian immune system to defend pathogen invasion or to resolve tissue damage. Dysregulation of inflammation contributes to the development of infectious diseases or inflammation-mediated chronic diseases such as obesity, diabetes, atherosclerosis, and cancer. Pattern-recognition receptors (PRRs) and their downstream regulators in the innate immune system function to trigger inflammation upon sensing molecular components from invading pathogens or damaged host cells. Better understanding of the regulation of PRR-mediated inflammation provides critical insights toward developing the treatment of infectious diseases and chronic inflammatory diseases. However, signaling networks underlying these PRR pathways still remain complicated and have much to be explored. Emerging evidence indicates that subcellular compartments or lipid organelles function as signaling platforms for conveying PRR signaling. Several cellular mediators of these subcellular organelles and vesicle trafficking have emerged to regulate the PPR pathways. In this review, we first highlight recent advances in the cell biology aspects of the Toll-like receptor (TLR) and cytosolic retinoic acid-inducible gene (RIG)-I-like receptor (RLR) pathways. We then focus on discussing a recently identified innate immune regulator called TBK1-associated protein in the endolysosomes (TAPE), also known as CC2D1A/Freud-1/Aki-1. TAPE is an endolysosomal adaptor shown to regulate the endosomal TLR3 and TLR4 pathways and the cytosolic RIG-I and melanoma differentiation-associated gene (MDA)-5 pathways at an early stage.