CARD9 Deficiencies Linked to Impaired Neutrophil Functions Against Phialophora verrucosa

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• 作者：Pin Liang ; Xiaowen Wang ; Runchao Wang ; Zhe Wan ; Wenling Han ; Ruoyu Li
• 关键词：Phialophora verrucosa ; CARD9 ; Neutrophil ; ROS ; Phagocytosis ; Pro ; inflammatory cytokines
• 刊名：Mycopathologia
• 出版年：2015
• 出版时间：June 2015
• 年：2015
• 卷：179
• 期：5-6
• 页码：347-357
• 全文大小：2,300 KB
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• 作者单位：Pin Liang (1) (2) (3)
  Xiaowen Wang (1) (2) (3)
  Runchao Wang (1) (2) (3)
  Zhe Wan (1) (2) (3)
  Wenling Han (4)
  Ruoyu Li (1) (2) (3)
  
  1. Department of Dermatology, Peking University First Hospital, Beijing, China
  2. Research Center for Medical Mycology, Peking University, Beijing, China
  3. Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, China
  4. Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Peking University Center for Human Disease Genomics, Key Laboratory of Medical Immunology, Ministry of Health, Beijing, China
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Microbiology
  Medical Microbiology
  Plant Sciences
  Microbial Ecology
  
• 出版者：Springer Netherlands
• ISSN：1573-0832

文摘

Caspase recruitment domain-containing protein 9 (CARD9) is an adaptor molecule that is critical for NF-κB activation and forms a complex with B cell lymphoma 10 and mucosa-associated lymphoid tissue lymphoma translocation gene 1 that mediates C-type lectin receptors (CLRs)-triggered intracellular signaling during antifungal immunity. However, the role of CARD9 in the host defense against Phialophora verrucosa (P. verrucosa) infection remains to be elucidated. In the present study, we investigated the functions of polymorphonuclear neutrophils (PMNs) from patients with CARD9 deficiencies against P. verrucosa. By isolating PMNs from patients and healthy blood donors and subsequently challenging the cells with P. verrucosa, we demonstrated that, compared with healthy donors, CARD9-deficient PMNs exhibited defects in P. verrucosa killing and pro-inflammatory cytokine productions, which can be rescued in the presence of serum; however, the CARD9-deficient PMNs exhibited normal reactive oxygen species generation and phagocytotic ability. In conclusion, our results indicate that CARD9 is indispensable for P. verrucosa killing by PMNs, and serum opsonization acts as a CARD9-independent way, which could be a promising immunotherapy in the future.