The tyrosine kinase Btk regulates the macrophage response to Listeria monocytogenes infection

PLoS One. 2013;8(3):e60476. doi: 10.1371/journal.pone.0060476. Epub 2013 Mar 27.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Animals
  • Bone Marrow Cells / pathology
  • Cytokines / biosynthesis
  • Disease Susceptibility
  • Enzyme Activation / drug effects
  • Immunoblotting
  • Lipopeptides / pharmacology
  • Listeria monocytogenes / drug effects
  • Listeria monocytogenes / physiology*
  • Listeriosis / enzymology*
  • Listeriosis / microbiology*
  • Listeriosis / pathology
  • MAP Kinase Signaling System / drug effects
  • Macrophages / drug effects
  • Macrophages / enzymology*
  • Macrophages / microbiology*
  • Mice
  • Phagocytosis / drug effects
  • Phagosomes / drug effects
  • Phagosomes / microbiology
  • Protein-Tyrosine Kinases / deficiency
  • Protein-Tyrosine Kinases / metabolism*

Substances

  • Cytokines
  • Lipopeptides
  • Pam(3)CSK(4) peptide
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • Btk protein, mouse