Journal
PLOS ONE
Volume 8, Issue 3, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0060476
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Funding
- Austrian Science Fund (FWF)/Medical University of Vienna [DK W1212]
- Austrian Science Fund [P19930]
- Medical University of Vienna
- University of Vienna
- Austrian Science Fund (FWF) [SFB F28]
- Austrian Science Fund (FWF) [P 23641] Funding Source: researchfish
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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-alpha, 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-gamma 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.
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