Human CARD9: A Critical Molecule of Fungal Immune Surveillance

Abstract

CARD9 is a signaling adaptor protein that is involved in the transduction of signals from a variety of innate pattern recognition receptors, including the C-type lectin receptors and intracellular NOD receptors and nucleic acid sensors. As a result, CARD9 has been shown in animal models to be an important regulator of immunity to bacteria, fungi, and viruses. Studies in humans with autosomal recessive CARD9 deficiency have indicated a highly specific role for this molecule in the activation of antifungal immune responses in the central nervous system, the oral mucosa, and the skin. Moreover, CARD9-dependent functions have recently been indicated to modulate the development of autoimmunity, inflammatory bowel diseases, and cancer. In this mini-review, we highlight the recent studies that have identified several novel functions of CARD9 in various disease contexts, and we summarize the contemporary understanding of the genetics and immunology of human CARD9 deficiency.

The microbiome and inflammatory bowel disease

“…21 Dectin-1 is a pattern recognition receptor that recognizes the components of the fungal cell wall. 45 CARD9 signaling occurs in response to the recognition of fungal ligands by Dectin-1. Alterations in Dectin-1 have been associated with medically refractory ulcerative colitis (UC).…”

“…46 CARD9 is also required for inflammatory cytokine production in response to specific bacterial stimuli and viral infection. 45 IL-6, TNF-a, and IL-1b are cytokines that are dependent on CARD9 function and are protective against fungal infection. 45 CARD9 knockout mice are susceptible to Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans among other fungi.…”

Myeloid-derived suppressor cells—new and exciting players in lung cancer

“…Caspase recruitment domain-containing protein 9 (CARD9) is mainly expressed in myeloid cells [58,59] and is an important adaptor protein in innate immunity, as it regulates innate immunity and affects adaptive immune responses [60,61]. Qu et al demonstrated the role of CARD9 in the development of LC for the first time.…”

Metabolism at the centre of the host–microbe relationship

“…Caspase recruitment domain-containing protein 9 (CARD9) is a signalling adaptor protein involved in integrating signals from a range of innate receptors, including REVIEW SERIES: TRANSLATING IMMUNOMETABOLISM C-type lectin and nucleotide-binding oligomerization domain-like (NOD) receptors, and is thus involved in bacterial, viral and fungal immune responses [106]. CARD9 deficiency was found to affect gut microbial composition and had a resultant effect on tryptophan metabolism [107].…”