A commentary on PTX3 is an extrinsic oncosuppressor regulating complement-dependent inflammation in cancer by Bonavita E, Gentile S, Rubino M, Maina V, Papait R, Kunderfranco P, et al.

Genetic deficiency of PTX3 affects the antifungal capacity of neutrophils and may contribute to the risk of invasive aspergillosis in patients treated with HSCT. (Funded by the European Society of Clinical Microbiology and Infectious Diseases and others.).

Invasive infections of the central nervous system or digestive tract caused by commensal fungi of the genus Candida are rare and life-threatening. The known risk factors include acquired and inherited immunodeficiencies, with patients often displaying a history of multiple infections. Cases of meningo-encephalitis and/or colitis caused by Candida remain unexplained. We studied five previously healthy children and adults with unexplained invasive disease of the central nervous system, or the digestive tract, or both, caused by Candida spp. The patients were aged 39, 7, 17 37, and 26 years at the time of infection and were unrelated but each born to consanguineous parents of Turkish (two patients), Iranian, Moroccan or Pakistani origin. Meningo-encephalitis was isolated in three patients, associated with colitis in a fourth patient, and the fifth patient suffered from isolated colitis. Inherited CARD9 deficiency was recently reported in otherwise healthy patients with other forms of severe disease caused by Candida, Trichophyton, Phialophora, and Exophiala, including meningo-encephalitis, but not colitis, caused by Candida and Exophiala. We therefore sequenced CARD9 in the five patients. All were found to be homozygous for rare and deleterious mutant CARD9 alleles: R70W and Q289* for the three patients with isolated C. albicans meningo-encephalitis, R35Q for the patient with meningo-encephalitis and colitis caused by C. glabrata, and Q295* for the patient with C. albicans colitis. Regardless of their levels of mutant CARD9 protein, the patients’ monocyte-derived dendritic cells responded poorly to CARD9-dependent fungal agonists (curdlan, heat-killed C. albicans, Saccharomyces cerevisiae and Exophiala dermatitidis). Invasive infections of the CNS or digestive tract caused by Candida in previously healthy children and even adults may be caused by inherited CARD9 deficiency.