caspase recruitment domain family member 9
The CARD9 gene provides instructions for making an immune system protein that is involved in the body's defense against fungal infections and is particularly important for fighting infection by a fungus called Candida. When the immune system recognizes Candida, it generates cells called Th17 cells. These cells produce signaling molecules (cytokines) called the interleukin-17 (IL-17) family as part of an immune process called the IL-17 pathway. The IL-17 pathway creates inflammation, sending other cytokines and white blood cells that fight foreign invaders and promote tissue repair. In addition, the IL-17 pathway promotes the production of certain antimicrobial protein segments (peptides) that control growth of Candida on the surface of mucous membranes.
In its role in defending against Candida on the mucous membranes and skin, the CARD9 protein passes along signals from other types of immune system proteins. Each of these proteins recognizes a different component of the Candida cell wall to trigger the production of Th17 cells and launch the immune response.
In addition to its role in protecting mucous membranes from fungal infection, the CARD9 protein is also important in recruiting neutrophils (immune cells that have strong anti-fungal activity) from the blood to protect the brain and other organs from fungal infection.
At least 15 CARD9 gene mutations have been identified in people with familial candidiasis, an inherited tendency to develop infections caused by the Candida fungus (commonly called yeast infections). Most people with familial candidiasis have chronic yeast infections of the skin, nails, and mucous membranes. This pattern of signs and symptoms, which is called chronic mucocutaneous candidiasis, typically begins in early childhood. People with familial candidiasis caused by CARD9 gene mutations can also develop systemic candidiasis, a potentially life-threatening condition in which Candida invades the blood and vital organs, especially the brain. Infections caused by additional types of fungi have also been identified in some people with this form of the disorder, which is sometimes called CARD9 deficiency.
Mutations in the CARD9 gene impair multiple signaling pathways that normally help recognize Candida and are thought to block (inhibit) the activity of the IL-17 pathway. Impairment of this pathway diminishes the body's immune response to Candida, leading to the chronic or recurrent yeast infections that occur in people with familial candidiasis. The mutations are also thought to impair the recruitment of neutrophils to fight Candida infection in the brain and other organs, which can lead to systemic candidiasis.