CARD9 Deficiencies Linked to Impaired Neutrophil Functions Against Phialophora verrucosa
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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.
KeywordsPhialophora verrucosa CARD9 Neutrophil ROS Phagocytosis Pro-inflammatory cytokines
The authors are grateful for the participation of the patients and healthy donors and the financial support of National Natural Science Foundation of China (Grant 81171510) and National Natural Science Foundation of China (Grant 81472890).
Conflict of interest
All the co-authors declare that they have no relevant conflicts of interest.
Written informed consent was obtained from all subjects, and the study was approved by the ethics committee of the Peking University First Hospital. Peripheral blood PMNs were isolated from venous blood specimens of patients and healthy blood donors, in accordance with the guidelines of the local ethical committee and the Declaration of Helsinki.
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