{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:43:29Z","timestamp":1791333809483,"version":"4.3.1"},"reference-count":78,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T00:00:00Z","timestamp":1630886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Bruton\u2019s tyrosine kinase (Btk) is a cytoplasmic kinase expressed in B cells and myeloid cells. It is essential for B cell development and natural antibody-mediated host defense against bacteria in humans and mice, but little is known about the role of Btk in innate host defense<jats:italic>in vivo<\/jats:italic>. Previous studies have indicated that lack of (natural) antibodies is paramount for impaired host defense against<jats:italic>Streptococcus (S.) pneumoniae<\/jats:italic>in patients and mice with a deficiency in functional Btk. In the present study, we re-examined the role of Btk in B cells and myeloid cells during pneumococcal pneumonia and sepsis in mice. The antibacterial defense of Btk<jats:sup>-\/-<\/jats:sup>mice was severely impaired during pneumococcal pneumosepsis and restoration of natural antibody production in Btk<jats:sup>-\/-<\/jats:sup>mice by transgenic expression of Btk specifically in B cells did not suffice to protect against infection. Btk<jats:sup>-\/-<\/jats:sup>mice with reinforced Btk expression in MhcII<jats:sup>+<\/jats:sup>cells, including B cells, dendritic cells and macrophages, showed improved antibacterial defense as compared to Btk<jats:sup>-\/-<\/jats:sup>mice. Bacterial outgrowth in Lysmcre-Btk<jats:sup>fl<\/jats:sup>\/Y mice was unaltered despite a reduced capacity of Btk-deficient alveolar macrophages to respond to pneumococci. Mrp8cre-Btk<jats:sup>fl<\/jats:sup>\/Y mice with a neutrophil specific paucity in Btk expression, however, demonstrated impaired antibacterial defense. Neutrophils of Mrp8cre-Btk<jats:sup>fl<\/jats:sup>\/Y mice displayed reduced release of granule content after pulmonary installation of lipoteichoic acid, a gram-positive bacterial cell wall component relevant for pneumococci. Moreover, Btk deficient neutrophils showed impaired degranulation and phagocytosis upon incubation with pneumococci<jats:italic>ex vivo<\/jats:italic>. Taken together, the results of our study indicate that besides regulating B cell-mediated immunity, Btk is critical for regulation of myeloid cell-mediated, and particularly neutrophil-mediated, innate host defense against<jats:italic>S. pneumoniae in vivo<\/jats:italic>.<\/jats:p>","DOI":"10.3389\/fimmu.2021.723967","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T19:47:33Z","timestamp":1630957653000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Bruton\u2019s Tyrosine Kinase-Mediated Signaling in Myeloid Cells Is Required for Protective Innate Immunity During Pneumococcal Pneumonia"],"prefix":"10.3389","volume":"12","author":[{"given":"Alexander P.","family":"de Porto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"de Beer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Florquin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joris J. 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