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.
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All data generated and analyzed during this study are included in the manuscript and supporting files.
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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.
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
