{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T07:38:31Z","timestamp":1776843511690,"version":"3.51.2"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Invasive candidiasis, most commonly caused by <jats:italic>Candida albicans<\/jats:italic>, poses a significant mortality risk and is challenging to treat. Non-tuberculous mycobacterial infections are opportunistic and linked to immune impairment. Caspase recruitment domain-containing protein 9 (CARD9) represents a class of proteins that incorporates the caspase recruitment domain, and its deficiency follows a strict autosomal recessive inheritance pattern, resulting in an impaired immune response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case presentation<\/jats:title><jats:p>A 51-year-old male who was admitted to the hospital 3 years ago because of recurrent fever accompanied by headache. The causative factor remains elusive and symptomatic treatment yielded unsatisfactory results. Next-generation sequencing (NGS) of cerebrospinal fluid (CSF) identified the fungus as <jats:italic>C. albicans<\/jats:italic>. Following antifungal therapy, the patient experienced relief from fever and headache; however, he subsequently developed a hydrocephalus. CSF culture indicated NTM\u2014<jats:italic>Mycobacterium intracellulare<\/jats:italic>, prompting the initiation of anti-NTM treatment. Given the recurrent infections, we collected peripheral blood for whole exome sequencing, which revealed a CARD9-deficient homozygote with a new mutation site identified as c.175C&amp;gt;T (p. Arg59Trp). The patient was hospitalized on 8 occasions for diagnostic assessment and treatment. Presently, antifungal treatment has been discontinued after 9 months of therapy, while anti-NTM therapy is being maintained, with the patient reporting no fever or other discomforts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The c.175C&amp;gt;T (p. Arg59Trp) mutation is a novel CARD9 gene mutation and is probably damaging. Clinicians should consider immune impairment as a contributing factor in the management of fungal infections among non-HIV\/AIDS patients. For such patients, conducting multiple CSF and blood cultures and employing new technologies such as NGS are advisable. Treatment of NTM and <jats:italic>C. albicans<\/jats:italic> requires personalized treatment plans. Moreover, the long-term follow-up should not be overlooked.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1648436","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T05:44:08Z","timestamp":1758087848000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Intracranial infections of Candida albicans and Mycobacterium intracellulare associated with CARD9 deficiency: case report and review of literature"],"prefix":"10.3389","volume":"16","author":[{"given":"Congchen","family":"Tang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoju","family":"Lv","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiangchao","family":"Long","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"57","DOI":"10.3390\/jof3040057","article-title":"Global and multi-national prevalence of fungal diseases-estimate precision","volume":"3","author":"Bongomin","year":"2017","journal-title":"J Fungi (Basel)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024198","article-title":"Epidemiology, species distribution, antifungal susceptibility and outcome of nosocomial candidemia in a tertiary care hospital in Italy","volume":"6","author":"Bassetti","year":"2011","journal-title":"PloS One"},{"key":"B3","doi-asserted-by":"publisher","first-page":"96380","DOI":"10.5662\/wjm.v14.i4.96380","article-title":"Relation between dysbiosis and inborn errors of immunity","volume":"14","author":"\u00d6zdemir","year":"2024","journal-title":"World J Methodol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1093\/ajcp\/65.6.991","article-title":"Pathobiologic features of human candidiasis. 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