SKAP2 is required for defense against <i>K. pneumoniae</i> infection and neutrophil respiratory burst.

Abstract

<i>Klebsiella pneumoniae</i> is a respiratory, blood, liver, and bladder pathogen of significant clinical concern. We show that the adaptor protein, SKAP2, is required for protection against <i>K. pneumoniae</i> (ATCC 43816) pulmonary infections. <i>Skap2-/</i>- mice had 100-fold higher bacterial burden when compared to wild-type and burden was controlled by SKAP2 expression in innate immune cells. <i>Skap2-/</i>- neutrophils and monocytes were present in infected lungs, and the neutrophils degranulated normally in response to <i>K. pneumoniae</i> infection in mice; however, <i>K. pneumoniae</i>-stimulated reactive oxygen species (ROS) production in vitro was abolished. <i>K. pneumoniae</i>-induced neutrophil ROS response required the activity of SFKs, Syk, Btk, PLCγ2, and PKC. The loss of SKAP2 significantly hindered the <i>K. pneumoniae</i>-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 <i>K. pneumoniae</i>-activated ROS production and for promoting bacterial clearance during infection.