- Please check and comment entries here.
caspase recruitment domain family member 9
1. Normal Function
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.
2. Health Conditions Related to Genetic Changes
2.1. Familial candidiasis
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.
3. Other Names for This Gene
- caspase recruitment domain family, member 9
This entry is adapted from https://medlineplus.gov/genetics/gene/card9
- Delsing CE, Bleeker-Rovers CP, Kullberg BJ, Netea MG. Treatment ofcandidiasis: insights from host genetics. Expert Rev Anti Infect Ther. 2012Aug;10(8):947-56. doi: 10.1586/eri.12.79. Review.
- Drewniak A, Gazendam RP, Tool AT, van Houdt M, Jansen MH, van Hamme JL, vanLeeuwen EM, Roos D, Scalais E, de Beaufort C, Janssen H, van den Berg TK,Kuijpers TW. Invasive fungal infection and impaired neutrophil killing in humanCARD9 deficiency. Blood. 2013 Mar 28;121(13):2385-92. doi:10.1182/blood-2012-08-450551.
- Drummond RA, Collar AL, Swamydas M, Rodriguez CA, Lim JK, Mendez LM, Fink DL, Hsu AP, Zhai B, Karauzum H, Mikelis CM, Rose SR, Ferre EM, Yockey L, Lemberg K,Kuehn HS, Rosenzweig SD, Lin X, Chittiboina P, Datta SK, Belhorn TH, Weimer ET,Hernandez ML, Hohl TM, Kuhns DB, Lionakis MS. CARD9-Dependent NeutrophilRecruitment Protects against Fungal Invasion of the Central Nervous System. PLoS Pathog. 2015 Dec 17;11(12):e1005293. doi: 10.1371/journal.ppat.1005293.
- Drummond RA, Lionakis MS. Mechanistic Insights into the Role of C-Type Lectin Receptor/CARD9 Signaling in Human Antifungal Immunity. Front Cell InfectMicrobiol. 2016 Apr 5;6:39. doi: 10.3389/fcimb.2016.00039.Review.
- Engelhardt KR, Grimbacher B. Mendelian traits causing susceptibility tomucocutaneous fungal infections in human subjects. J Allergy Clin Immunol. 2012Feb;129(2):294-305; quiz 306-7. doi: 10.1016/j.jaci.2011.12.966. Review.
- Filler SG. Insights from human studies into the host defense againstcandidiasis. Cytokine. 2012 Apr;58(1):129-32. doi: 10.1016/j.cyto.2011.09.018.
- Glocker E, Grimbacher B. Chronic mucocutaneous candidiasis and congenitalsusceptibility to Candida. Curr Opin Allergy Clin Immunol. 2010 Dec;10(6):542-50.doi: 10.1097/ACI.0b013e32833fd74f. Review.
- Lanternier F, Mahdaviani SA, Barbati E, Chaussade H, Koumar Y, Levy R, DenisB, Brunel AS, Martin S, Loop M, Peeters J, de Selys A, Vanclaire J, Vermylen C,Nassogne MC, Chatzis O, Liu L, Migaud M, Pedergnana V, Desoubeaux G, Jouvion G,Chretien F, Darazam IA, Schäffer AA, Netea MG, De Bruycker JJ, Bernard L, Reynes J, Amazrine N, Abel L, Van der Linden D, Harrison T, Picard C, Lortholary O,Mansouri D, Casanova JL, Puel A. Inherited CARD9 deficiency in otherwise healthy children and adults with Candida species-induced meningoencephalitis, colitis, orboth. J Allergy Clin Immunol. 2015 Jun;135(6):1558-68.e2. doi:10.1016/j.jaci.2014.12.1930.
- Plantinga TS, Johnson MD, Scott WK, Joosten LA, van der Meer JW, Perfect JR,Kullberg BJ, Netea MG. Human genetic susceptibility to Candida infections. MedMycol. 2012 Nov;50(8):785-94. doi: 10.3109/13693786.2012.690902.Review.
- Smeekens SP, van de Veerdonk FL, Kullberg BJ, Netea MG. Genetic susceptibilityto Candida infections. EMBO Mol Med. 2013 Jun;5(6):805-13. doi:10.1002/emmm.201201678.