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Publication : Neutrophils require SKAP2 for reactive oxygen species production following C-type lectin and <i>Candida</i> stimulation.

First Author  Nguyen GT Year  2021
Journal  iScience Volume  24
Issue  8 Pages  102871
PubMed ID  34386732 Mgi Jnum  J:328636
Mgi Id  MGI:6828573 Doi  10.1016/j.isci.2021.102871
Citation  Nguyen GT, et al. (2021) Neutrophils require SKAP2 for reactive oxygen species production following C-type lectin and Candida stimulation. iScience 24(8):102871
abstractText  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.
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