title: The tyrosine kinase Btk regulates the macrophage response to Listeria monocytogenes infection.
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.
authors.affiliation: Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Afitap Derya
authors.initials: AD
authors.lastname: Köprülü
authors.forename: Renate
authors.initials: R
authors.lastname: Kastner
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wienerroither
authors.forename: Caroline
authors.initials: C
authors.lastname: Lassnig
authors.forename: Eva Maria
authors.initials: EM
authors.lastname: Putz
authors.forename: Olivia
authors.initials: O
authors.lastname: Majer
authors.forename: Benjamin
authors.initials: B
authors.lastname: Reutterer
authors.forename: Veronika
authors.initials: V
authors.lastname: Sexl
authors.forename: Karl
authors.initials: K
authors.lastname: Kuchler
authors.forename: Mathias
authors.initials: M
authors.lastname: Müller
authors.forename: Thomas
authors.initials: T
authors.lastname: Decker
authors.forename: Wilfried
authors.initials: W
authors.lastname: Ellmeier
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D004198:Disease Susceptibility; D004789:Enzyme Activation / Q000187:drug effects; D015151:Immunoblotting; D055666:Lipopeptides / Q000494:pharmacology; D008089:Listeria monocytogenes / Q000187:drug effects / Q000502:physiology*; D008088:Listeriosis / Q000201:enzymology* / Q000382:microbiology* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology* / Q000382:microbiology*; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects; D010588:Phagosomes / Q000187:drug effects / Q000382:microbiology; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000378:metabolism*
chemical_list: D016207:Cytokines; D055666:Lipopeptides; C508075:Pam(3)CSK(4) peptide; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse
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