Purpose of review: The present review discusses the physiological functions of selected caspase recruitment domain (CARD)-containing sensor and adaptor proteins and their role in the pathogenesis of intestinal diseases.
Recent findings: Myeloid and lymphoid cells as well as intestinal epithelial cells express several intracellular CARD-containing proteins. CARD-containing sensors, particularly NOD1 (CARD4), NOD2 (CARD15) and IPAF (CARD12), have an important role in the detection of conserved microbial structures of invading microbial pathogens. Upon ligand recognition and activation, the sensors interact through CARD domains with downstream CARD-containing adaptors including CARD9, RIP2 (CARD3) and ASC (CARD5). Recent data suggest that multiple signaling pathways from Toll-like receptors and non-Toll-receptor pathways converge on these adaptor proteins and that their functions are crucial for the initiation of innate immune responses to invading microbial pathogens.
Summary: CARD-containing adaptors and sensors represent an important family of molecules involved in innate host defense against gastrointestinal pathogens and in the regulation of inflammatory responses, suggesting that further insights into their physiological functions may yield new pharmacological strategies for treating intestinal inflammatory conditions.