Neutrophils require SKAP2 for reactive oxygen species production following C-type lectin and Candida stimulation.

Neutrophils require SKAP2 for reactive oxygen species production following C-type lectin and Candida stimulation.
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中性粒细胞在c型凝集素和念珠菌刺激后需要SKAP2来产生活性氧。

DOI:
10.1016/j.isci.2021.102871
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发表时间:
2021-08-20
期刊:
影响因子:
5.8
通讯作者:
Mecsas J
Mecsas J
中科院分区:
综合性期刊2区
文献类型:
--
作者:
Nguyen GT;Xu S;Adams W;Leong JM;Bunnell SC;Mansour MK;Sykes DB;Mecsas J

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Signaling cascades converting the recognition of pathogens to efficient inflammatory responses by neutrophils are critical for host survival. SKAP2, an adaptor protein, is required for reactive oxygen species (ROS) generation following neutrophil stimulation by integrins, formyl peptide receptors, and for host defense against the Gram-negative bacterial pathogens, Klebsiella pneumoniae and Yersinia pseudotuberculosis. Using neutrophils from murine HoxB8-immortalized progenitors, we show that SKAP2 in neutrophils is crucial for maximal ROS response to purified C-type lectin receptor agonists and to the fungal pathogens, Candida glabrata and Candida albicans, and for robust killing of C. glabrata. Inside-out signaling to integrin and Syk phosphorylation occurred independently of SKAP2 after Candida infection. However, Pyk2, ERK1/2, and p38 phosphorylation were significantly reduced after infection with C. glabrata and K. pneumoniae in Skap2−/− neutrophils. These data demonstrate the importance of SKAP2 in ROS generation and host defense beyond antibacterial immunity to include CLRs and Candida species. SKAP-2 regulates neutrophil ROS following C-type lectin stimulation SKAP-2 is required for C. glabrata-stimulated neutrophil ROS and killing Candida and Klebsiella-induced activation of Pyk2, pERK1/2, and p38 requires SKAP-2 Neutrophils require SKAP-2 to control K. pneumoniae infection Biological sciences; Cell biology; Immunology; Microbiology
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