Vornholz, L. and Ruland, J. (2020). Curr Top Microbiol Immunol 429, 177-203.
Caspase recruitment domain protein 9 (CARD9) forms essential signaling complexes in the innate immune system that integrate cues from C-type lectin receptors and specific intracellular pattern recognition receptors. These CARD9-mediated signals are pivotal for host defense against fungi, and they mediate immunity against certain bacteria, viruses and parasites. Furthermore, CARD9-regulated pathways are involved in sterile inflammatory responses critical for immune homeostasis and can control pro- and antitumor immunity in cancer microenvironments. Consequently, multiple genetic alterations of human CARD9 are connected to primary immunodeficiencies or prevalent inflammatory disorders in patients. This review will summarize our current understanding of CARD9 signaling in the innate immune system, its physiological and pathological functions and their implications for human immune-mediated diseases.