title: Impaired Toll-like receptor 8-mediated IL-6 and TNF-alpha production in antigen-presenting cells from patients with X-linked agammaglobulinemia.
abstract: The critical role of Bruton tyrosine kinase (Btk) in B cells has been documented by the block of B-cell development in X-linked agammaglobulinemia (XLA). Less is known about Btk function in myeloid cells. Several pieces of evidence indicate that Btk is a component of Toll-like receptor (TLR) signaling. We analyzed whether Btk deficiency in XLA is associated with an impaired dendritic cell (DC) compartment or defective TLR signaling. We analyzed the expression of TLRs 1 to 9 on myeloid DCs generated from XLA patients and evaluated their response to activation by specific TLR agonists. We show that XLA patients have normal numbers of circulating DCs. Btk-deficient DCs have no defect in response to stimulation of TLRs 1/2, 2/6, 3, 4, and 5 but display a profound impairment of IL-6 and TNF-alpha production in response to stimulation by TLR-8 cognate agonist, ssRNA. These findings may provide an explanation for the susceptibility to enteroviral infections in XLA patients.
authors.affiliation: Institute of Immunology, Charles University, 2nd Medical School, Prague, Czech Republic.
authors.forename: Klára
authors.initials: K
authors.lastname: Sochorová
authors.forename: Rudolf
authors.initials: R
authors.lastname: Horváth
authors.forename: Daniela
authors.initials: D
authors.lastname: Rozková
authors.forename: Jirí
authors.initials: J
authors.lastname: Litzman
authors.forename: Jirina
authors.initials: J
authors.lastname: Bartunková
authors.forename: Anna
authors.initials: A
authors.lastname: Sedivá
authors.forename: Radek
authors.initials: R
authors.lastname: Spísek
mesh_terms: D000361:Agammaglobulinemia / Q000378:metabolism*; D000938:Antigen-Presenting Cells / Q000378:metabolism*; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D051200:Toll-Like Receptor 8 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D015850:Interleukin-6; C495349:TLR8 protein, human; D051200:Toll-Like Receptor 8; D014409:Tumor Necrosis Factor-alpha