摘要：SummarySignaling 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 pneumoniaeandYersinia 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 glabrataandCandida albicans, and for robust killing ofC. glabrata. Inside-out signaling to integrin and Syk phosphorylation occurred independently of SKAP2 afterCandidainfection. However, Pyk2, ERK1/2, and p38 phosphorylation were significantly reduced after infection withC. glabrataandK. pneumoniaeinSkap2−/−neutrophils. These data demonstrate the importance of SKAP2 in ROS generation and host defense beyond antibacterial immunity to include CLRs andCandidaspecies.Graphical abstractDisplay OmittedHighlights•SKAP-2 regulates neutrophil ROS following C-type lectin stimulation•SKAP-2 is required forC. glabrata-stimulated neutrophil ROS and killing•CandidaandKlebsiella-induced activation of Pyk2, pERK1/2, and p38 requires SKAP-2•Neutrophils require SKAP-2 to controlK. pneumoniaeinfectionBiological sciences; Cell biology; Immunology; Microbiology
