Abstract：
Patients with caspase-associated recruitment domain-9 (CARD9) deficiency are more likely to develop invasive fungal disease that affect CNS. However, the understanding of how Candida invades and persists in CNS is still limited. We here reported a 24-year-old woman who were previously immunocompetent and diagnosed with CNS candidiasis. A novel autosomal recessive homozygous CARD9 mutation (c.184 + 5G > T) from this patient was identified using whole genomic sequencing. Furthermore, we extensively characterized the impact of this CARD9 mutation on the host immune response in monocytes, neutrophils and CD4 + T cells, using single cell sequencing and in vitro experiments. Decreased pro-inflammatory cytokine productions of CD14 + monocyte, impaired Th17 cell differentiation, and defective neutrophil accumulation in CNS were found in this patient. In conclusion, this study proposed a novel mechanism of CNS candidiasis development. Patients with CNS candidiasis in absence of known immunodeficiencies should be analyzed for CARD9 gene mutation as the cause of invasive fungal infection predisposition.
摘要：
caspase相关募集结构域-9（CARD9）缺乏的患者更有可能发展为侵袭性真菌病，影响中枢神经系统。然而,对念珠菌如何侵入中枢神经系统并持续存在的理解仍然有限.我们在这里报道了一名24岁的女性，她先前具有免疫能力并被诊断患有中枢神经系统念珠菌病。使用全基因组测序鉴定了来自该患者的新型常染色体隐性纯合CARD9突变(c.184+5G>T)。此外，我们广泛表征了这种CARD9突变对单核细胞中宿主免疫反应的影响，中性粒细胞和CD4+T细胞，使用单细胞测序和体外实验。CD14+单核细胞的促炎细胞因子产生减少，Th17细胞分化受损，在该患者中发现中枢神经系统中性粒细胞积累缺陷。总之,这项研究提出了中枢神经系统念珠菌病发展的新机制。没有已知免疫缺陷的中枢神经系统念珠菌病患者应分析CARD9基因突变作为侵袭性真菌感染易感性的原因。
