CARD9 Signaling in the Innate Immune Response

CARD9 is a caspase recruitment domain-containing signaling protein that is highly expressed in dendritic cells and in macrophages. Work over the last two years has identified CARD9 as a central regulator of innate immunity. Best characterized is CARD9's function downstream of ITAM-bearing or ITAM-coupled receptors in myeloid cells, including its essential role downstream of the antifungal pattern-recognition receptor Dectin-1. In the ITAM receptor pathway, CARD9 couples receptor proximal splenic tyrosine kinase SYK activation to the canonical NF-kappa B pathway. In addition, CARD9 is involved in the activation of p38 and JNK kinases and it can function downstream of cytosolic pattern-recognition receptors. CARD9 signaling mediates mammalian innate immune responses against selected fungi, bacteria, and viruses and can prime and shape adaptive immunity. This review will summarize current: knowledge on CARD9 signaling and its function in the innate immune response.