title: CARD9 deficiencies linked to impaired neutrophil functions against Phialophora verrucosa.
abstract: 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.
authors: Department of Dermatology, Peking University First Hospital, Beijing, China.
authors: Pin
authors: P
authors: Liang
authors: Xiaowen
authors: X
authors: Wang
authors: Runchao
authors: R
authors: Wang
authors: Zhe
authors: Z
authors: Wan
authors: Wenling
authors: W
authors: Han
authors: Ruoyu
authors: R
authors: Li
mesh_terms: D053468:CARD Signaling Adaptor Proteins / Q000172:deficiency*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D050296:Microbial Viability; D009181:Mycoses / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology; D009504:Neutrophils / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis; D010676:Phialophora / Q000302:isolation & purification*
chemical_list: D053468:CARD Signaling Adaptor Proteins; C505855:CARD9 protein, human; D016207:Cytokines; D009569:Nitric Oxide