Publication details

Impaired Toll-like receptor 8-mediated IL-6 and TNF-alpha production in antigen-presenting cells from patients with X-linked agammaglobulinemia

Authors

SOCHOROVÁ Klára HORVÁTH R. ROZKOVÁ D. LITZMAN Jiří BARTŮŇKOVÁ Jiřina ŠEDIVÁ Anna SPÍŠEK Radek

Year of publication 2007
Type Article in Periodical
Magazine / Source Blood
MU Faculty or unit

Faculty of Medicine

Citation
Field Immunology
Keywords Toll-like receptor; Brutons tyrosine kinase; antigen-presenting cells
Description 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.

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