Bruton’s Tyrosine Kinase in Neutrophils Is Crucial for Host Defense against <b><i>Klebsiella pneumoniae</i></b>

Abstract

Humans with dysfunctional Bruton’s tyrosine kinase (Btk) are highly susceptible to bacterial infections. Compelling evidence indicates that Btk is essential for B cell-mediated immunity, whereas its role in myeloid cell-mediated immunity against infections is controversial. In this study, we determined the contribution of Btk in B cells and neutrophils to host defense against the extracellular bacterial pathogen <i>Klebsiella pneumoniae</i>, a common cause of pulmonary infections and sepsis. <i>Btk</i>^−/− mice were highly susceptible to <i>Klebsiella</i> infection, which was not reversed by Btk re-expression in B cells and restoration of natural antibody levels. Neutrophil-specific Btk deficiency impaired host defense against <i>Klebsiella</i> to a similar extent as complete Btk deficiency. Neutrophil-specific Btk deficiency abolished extracellular reactive oxygen species production in response to <i>Klebsiella</i>. These data indicate that expression of Btk in neutrophils is crucial, while in B cells, it is dispensable for in vivo host defense against <i>K. pneumoniae</i>.