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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.

SUBMITTER: Liu Z 

PROVIDER: S-EPMC10643901 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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

Liu Zhe Z   De Porto Alexander P N A APNA   De Beer Regina R   Roelofs Joris J T H JJTH   De Boer Onno J OJ   Florquin Sandrine S   Van't Veer Cornelis C   Hendriks Rudi W RW   Van der Poll Tom T   De Vos Alex F AF  

Journal of innate immunity 20220510 1


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-/- mic  ...[more]

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