Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Abstract
Background
Liver kinase B1 (Lkb1, gene name
Stk11
) functions as a tumor suppressor in cancer. Myeloid cell Lkb1 potentiates lung inflammation induced by the Gram-negative bacterial cell wall component lipopolysaccharide and in host defense during Gram-negative pneumonia. Here, we sought to investigate the role of myeloid Lkb1 in lung inflammation elicited by the Gram-positive bacterial cell wall component lipoteichoic acid (LTA) and during pneumonia caused by the Gram-positive respiratory pathogen
Streptococcus pneumoniae
(
Spneu
).
Methods
Alveolar and bone marrow derived macrophages (AMs, BMDMs) harvested from myeloid-specific Lkb1 deficient (
Stk11
-ΔM) and littermate control mice were stimulated with LTA or
Spneu
in vitro.
Stk11
-ΔM and control mice were challenged via the airways with LTA or infected with
Spneu
in vivo.
Results
Lkb1 deficient AMs and BMDMs produced less tumor necrosis factor (TNF)α upon activation by LTA or
Spneu.
During LTA-induced lung inflammation,
Stk11
-ΔM mice had reduced numbers of AMs in the lungs, as well as diminished cytokine release and neutrophil recruitment into the airways. During pneumonia induced by either encapsulated or non-encapsulated
Spneu
,
Stk11
-ΔM and control mice had comparable bacterial loads and inflammatory responses in the lung
,
with the exception of lower TNFα levels in
Stk11
-ΔM mice after infection with the non-encapsulated strain.
Conclusion
Myeloid Lkb1 contributes to LTA-induced lung inflammation, but is not important for host defense during pneumococcal pneumonia.