Nguyen, Giang T. and Shaban, Lamyaa and Mack, Matthias and Swanson, Kenneth D. and Bunnell, Stephen C. and Sykes, David B. and Mecsas, Joan (2020) SKAP2 is required for defense against K. pneumoniae infection and neutrophil respiratory burst. ELIFE, 9: e56656. ISSN 2050-084X,
Full text not available from this repository. (Request a copy)Abstract
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, PLC gamma 2, 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TYROSINE KINASE SYK; PULMONARY HOST-DEFENSE; KLEBSIELLA-PNEUMONIAE; BACTERIAL CLEARANCE; PROTEIN; ADHESION; SRC; ACTIVATION; RECRUITMENT; MACROPHAGES; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Mar 2021 05:26 |
| Last Modified: | 26 Mar 2021 05:26 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44684 |
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