The Tyrosine Kinase Btk Regulates the Macrophage Response to Listeria monocytogenes Infection
نویسندگان
چکیده
In this study we investigated the role of Bruton's tyrosine kinase (Btk) in the immune response to the Gram-positive intracellular bacterium Listeria monocytogenes (Lm). In response to Lm infection, Btk was activated in bone marrow-derived macrophages (BMMs) and Btk (-/-) BMMs showed enhanced TNF-α, IL-6 and IL-12p40 secretion, while type I interferons were produced at levels similar to wild-type (wt) BMMs. Although Btk-deficient BMMs displayed reduced phagocytosis of E. coli fragments, there was no difference between wt and Btk (-/-) BMMs in the uptake of Lm upon infection. Moreover, there was no difference in the response to heat-killed Lm between wt and Btk (-/-) BMMs, suggesting a role for Btk in signaling pathways that are induced by intracellular Lm. Finally, Btk (-/-) mice displayed enhanced resistance and an increased mean survival time upon Lm infection in comparison to wt mice. This correlated with elevated IFN-γ and IL-12p70 serum levels in Btk (-/-) mice at day 1 after infection. Taken together, our data suggest an important regulatory role for Btk in macrophages during Lm infection.
منابع مشابه
STK receptor tyrosine kinase regulates susceptibility to infection with Listeria monocytogenes.
We have previously identified the STK receptor tyrosine kinase as a key regulator of macrophage activation and cell-mediated immune responses. Here we demonstrate that, although MSP activation of STK inhibits NO production by macrophages in response to heat-killed Listeria monocytogenes, STK-deficient mice exhibit increased susceptibility to infection with Listeria.
متن کاملMitogen-activated protein kinase-activated protein kinase 2-deficient mice show increased susceptibility to Listeria monocytogenes infection.
Mitogen-activated protein kinase-activated protein kinase 2 (MK2) is one of several kinases activated through direct phosphorylation by p38 mitogen-activated protein kinase. MK2 regulates LPS-induced TNF mRNA translation, and targeted mutation of the MK2 gene renders mice more resistant to D-galactosamine plus LPS-induced liver damage. In the present study, we investigated the role of MK2 in im...
متن کاملMitogen-Activated Protein Kinase-Activated Protein Kinase 2-Deficien Mice Show Increased Susceptibility to Listeria monocytogenes Infection
Mitogen-activated protein kinase-activated protein kinase 2 (MK2) is one of several kinases activated through direct phosphorylation by p38 mitogen-activated protein kinase. MK2 regulates LPS-induced TNF mRNA translation, and targeted mutation of the MK2 gene renders mice more resistant to D-galactosamine plus LPS-induced liver damage. In the present study, we investigated the role of MK2 in im...
متن کاملDeficient Expression of Bruton's Tyrosine Kinase in Monocytes from X-Linked Agammaglobulinemia as Evaluated by a Flow Cytometric Analysis and its Clinical Application to Carrier Detection
Background: The B-cell defect in X-linked agammaglobulinemia (XLA) is caused by mutations in the gene for Bruton's tyrosine kinase (BTK). BTK mutations result in deficient expression of BTK protein in peripheral blood monocytes. Methods: Using the anti-BTK monoclonal antibody (48-2H), a flow cytometric analysis of intra cytoplasmic BTK protein expression in monocytes was performed to identify I...
متن کاملListeria monocytogenes modulates macrophage cytokine responses through STAT serine phosphorylation and the induction of suppressor of cytokine signaling 3.
Macrophage activation as part of natural resistance to infection is caused by stimulation with IFN-gamma and by the invading microorganisms or microbial products. Infection of macrophages with the Gram-positive bacterium Listeria monocytogenes for short periods before activation with IFN-gamma increased the phosphorylation of transcription factor STAT1 at S727 and thereby the expression of IFN-...
متن کامل