Bruton's Tyrosine Kinase in Neutrophils Is Crucial for Host Defense against Klebsiella pneumoniae

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 Klebsiella pneumoniae, a common cause of pulmonary infections and sepsis. Btk-/- mice were highly susceptible to Klebsiella 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 Klebsiella to a similar extent as complete Btk deficiency. Neutrophil-specific Btk deficiency abolished extracellular reactive oxygen species production in response to Klebsiella. These data indicate that expression of Btk in neutrophils is crucial, while in B cells, it is dispensable for in vivo host defense against K. pneumoniae.

Keywords: Bruton’s tyrosine kinase; Innate immunity; Klebsiella pneumoniae; Neutrophils; Reactive oxygen species.