SKAP2 is required for defense against K. pneumoniae infection and neutrophil respiratory burst
- Tufts Graduate School of Biomedical Sciences, United States
- University Hospital Regensburg, Germany
- Beth Israel Deaconess Medical Center, United States
- Tufts University School of Medicine, United States
- Massachusetts General Hospital, United States
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, PLCg2, and PKCs. 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.
Data availability
All data generated and analyzed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
National Institutes of Health (R01 AI113166)
- Joan Mecsas
National Institutes of Health (4T32AI007422)
- Lamyaa Shaban
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal experimental procedures followed NIH guidelines. All mice were handled in accordance with protocols (B2018-10) approved by the Institutional Animal Care and Use Committee (IACUC) of Tufts University.
Reviewing Editor
- Christina L Stallings, Washington University School of Medicine, United States
Publication history
- Received: March 5, 2020
- Accepted: April 29, 2020
- Accepted Manuscript published: April 30, 2020 (version 1)
- Version of Record published: May 26, 2020 (version 2)
Copyright
© 2020, Nguyen et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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SKAP2 is required for defense against K. pneumoniae infection and neutrophil respiratory burst
eLife 9:e56656.
https://doi.org/10.7554/eLife.56656
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