Bruton’s Tyrosine Kinase in Neutrophils Is Crucial for Host Defense against Klebsiella pneumoniae
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 determi...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Karger Publishers
2022-05-01
|
| Series: | Journal of Innate Immunity |
| Subjects: | |
| Online Access: | https://www.karger.com/Article/FullText/524583 |
| _version_ | 1828724896043106304 |
|---|---|
| author | Zhe Liu Alexander P.N.A. De Porto Regina De Beer Joris J.T.H. Roelofs Onno J. De Boer Sandrine Florquin Cornelis Van’t Veer Rudi W. Hendriks Tom Van der Poll Alex F. De Vos |
| author_facet | Zhe Liu Alexander P.N.A. De Porto Regina De Beer Joris J.T.H. Roelofs Onno J. De Boer Sandrine Florquin Cornelis Van’t Veer Rudi W. Hendriks Tom Van der Poll Alex F. De Vos |
| author_sort | Zhe Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T13:17:36Z |
| format | Article |
| id | doaj.art-9a182f02185d4c06a7e0960e061482bc |
| institution | Directory Open Access Journal |
| issn | 1662-811X 1662-8128 |
| language | English |
| last_indexed | 2024-04-12T13:17:36Z |
| publishDate | 2022-05-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Journal of Innate Immunity |
| spelling | doaj.art-9a182f02185d4c06a7e0960e061482bc2022-12-22T03:31:39ZengKarger PublishersJournal of Innate Immunity1662-811X1662-81282022-05-0111510.1159/000524583524583Bruton’s Tyrosine Kinase in Neutrophils Is Crucial for Host Defense against Klebsiella pneumoniaeZhe Liu0Alexander P.N.A. De Porto1https://orcid.org/0000-0002-1201-0754Regina De Beer2Joris J.T.H. Roelofs3Onno J. De Boer4https://orcid.org/0000-0001-8844-1326Sandrine Florquin5Cornelis Van’t Veer6Rudi W. Hendriks7Tom Van der Poll8Alex F. De Vos9Center for Experimental and Molecular Medicine, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The NetherlandsAmsterdam Infection and Immunity Institute (AI&II), Amsterdam UMC, Amsterdam, The NetherlandsDepartment of Pathology, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The NetherlandsDepartment of Pathology, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The NetherlandsDepartment of Pulmonary Medicine, Erasmus MC, University Medical Center, Rotterdam, The NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The NetherlandsHumans 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.https://www.karger.com/Article/FullText/524583bruton’s tyrosine kinaseklebsiella pneumoniaeinnate immunityneutrophilsreactive oxygen species |
| spellingShingle | Zhe Liu Alexander P.N.A. De Porto Regina De Beer Joris J.T.H. Roelofs Onno J. De Boer Sandrine Florquin Cornelis Van’t Veer Rudi W. Hendriks Tom Van der Poll Alex F. De Vos Bruton’s Tyrosine Kinase in Neutrophils Is Crucial for Host Defense against Klebsiella pneumoniae Journal of Innate Immunity bruton’s tyrosine kinase klebsiella pneumoniae innate immunity neutrophils reactive oxygen species |
| title | Bruton’s Tyrosine Kinase in Neutrophils Is Crucial for Host Defense against Klebsiella pneumoniae |
| title_full | Bruton’s Tyrosine Kinase in Neutrophils Is Crucial for Host Defense against Klebsiella pneumoniae |
| title_fullStr | Bruton’s Tyrosine Kinase in Neutrophils Is Crucial for Host Defense against Klebsiella pneumoniae |
| title_full_unstemmed | Bruton’s Tyrosine Kinase in Neutrophils Is Crucial for Host Defense against Klebsiella pneumoniae |
| title_short | Bruton’s Tyrosine Kinase in Neutrophils Is Crucial for Host Defense against Klebsiella pneumoniae |
| title_sort | bruton s tyrosine kinase in neutrophils is crucial for host defense against klebsiella pneumoniae |
| topic | bruton’s tyrosine kinase klebsiella pneumoniae innate immunity neutrophils reactive oxygen species |
| url | https://www.karger.com/Article/FullText/524583 |
| work_keys_str_mv | AT zheliu brutonstyrosinekinaseinneutrophilsiscrucialforhostdefenseagainstklebsiellapneumoniae AT alexanderpnadeporto brutonstyrosinekinaseinneutrophilsiscrucialforhostdefenseagainstklebsiellapneumoniae AT reginadebeer brutonstyrosinekinaseinneutrophilsiscrucialforhostdefenseagainstklebsiellapneumoniae AT jorisjthroelofs brutonstyrosinekinaseinneutrophilsiscrucialforhostdefenseagainstklebsiellapneumoniae AT onnojdeboer brutonstyrosinekinaseinneutrophilsiscrucialforhostdefenseagainstklebsiellapneumoniae AT sandrineflorquin brutonstyrosinekinaseinneutrophilsiscrucialforhostdefenseagainstklebsiellapneumoniae AT cornelisvantveer brutonstyrosinekinaseinneutrophilsiscrucialforhostdefenseagainstklebsiellapneumoniae AT rudiwhendriks brutonstyrosinekinaseinneutrophilsiscrucialforhostdefenseagainstklebsiellapneumoniae AT tomvanderpoll brutonstyrosinekinaseinneutrophilsiscrucialforhostdefenseagainstklebsiellapneumoniae AT alexfdevos brutonstyrosinekinaseinneutrophilsiscrucialforhostdefenseagainstklebsiellapneumoniae |