In:
Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-9-6)
Abstract:
Bruton’s 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 in vivo . Previous studies have indicated that lack of (natural) antibodies is paramount for impaired host defense against Streptococcus (S.) pneumoniae 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 -/- mice was severely impaired during pneumococcal pneumosepsis and restoration of natural antibody production in Btk -/- mice by transgenic expression of Btk specifically in B cells did not suffice to protect against infection. Btk -/- mice with reinforced Btk expression in MhcII + cells, including B cells, dendritic cells and macrophages, showed improved antibacterial defense as compared to Btk -/- mice. Bacterial outgrowth in Lysmcre-Btk fl /Y mice was unaltered despite a reduced capacity of Btk-deficient alveolar macrophages to respond to pneumococci. Mrp8cre-Btk fl /Y mice with a neutrophil specific paucity in Btk expression, however, demonstrated impaired antibacterial defense. Neutrophils of Mrp8cre-Btk fl /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 ex vivo . 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 S. pneumoniae in vivo .
Type of Medium:
Online Resource
ISSN:
1664-3224
DOI:
10.3389/fimmu.2021.723967
DOI:
10.3389/fimmu.2021.723967.s001
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2021
detail.hit.zdb_id:
2606827-8
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