TY - JOUR
T1 - Bruton's Tyrosine Kinase in Neutrophils Is Crucial for Host Defense against Klebsiella pneumoniae
AU - Liu, Zhe
AU - de Porto, Alexander P. N. A.
AU - de Beer, Regina
AU - Roelofs, Joris J. T. H.
AU - de Boer, Onno J.
AU - Florquin, Sandrine
AU - van't Veer, Cornelis
AU - Hendriks, Rudi W.
AU - van der Poll, Tom
AU - de Vos, Alex F.
N1 - Funding Information: Zhe Liu was funded by the Chinese Scholarship Council (CSC No. 201706170060). Alexander P.N.A. De Porto was funded by a PhD scholarship from the Academic Medical Center, Amsterdam, the Netherlands. Publisher Copyright: © 2022
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Bruton's tyrosine kinase
KW - Innate immunity
KW - Klebsiella pneumoniae
KW - Neutrophils
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=85130464695&partnerID=8YFLogxK
U2 - https://doi.org/10.1159/000524583
DO - https://doi.org/10.1159/000524583
M3 - Article
C2 - 35537415
SN - 1662-811X
JO - Journal of innate immunity
JF - Journal of innate immunity
ER -