| First Author | Nguyen GT | Year | 2020 |
| Journal | Elife | Volume | 9 |
| PubMed ID | 32352382 | Mgi Jnum | J:290303 |
| Mgi Id | MGI:6442267 | Doi | 10.7554/eLife.56656 |
| Citation | Nguyen GT, et al. (2020) SKAP2 is required for defense against K. pneumoniae infection and neutrophil respiratory burst. Elife 9:e56656 |
| abstractText | Klebsiella pneumoniae is a respiratory, blood, liver, and bladder pathogen of significant clinical concern. We show that the adaptor protein, SKAP2, is required for protection against K. pneumoniae (ATCC 43816) pulmonary infections. Skap2-/- mice had 100-fold higher bacterial burden when compared to wild-type and burden was controlled by SKAP2 expression in innate immune cells. Skap2-/- neutrophils and monocytes were present in infected lungs, and the neutrophils degranulated normally in response to K. pneumoniae infection in mice; however, K. pneumoniae-stimulated reactive oxygen species (ROS) production in vitro was abolished. K. pneumoniae-induced neutrophil ROS response required the activity of SFKs, Syk, Btk, PLCgamma2, and PKC. The loss of SKAP2 significantly hindered the K. pneumoniae-induced phosphorylation of SFKs, Syk, and Pyk2 implicating SKAP2 as proximal to their activation in pathogen-signaling pathways. In conclusion, SKAP2-dependent signaling in neutrophils is essential for K. pneumoniae-activated ROS production and for promoting bacterial clearance during infection. |
