Myeloid liver kinase B1 contributes to lung inflammation induced by lipoteichoic acid but not by viable Streptococcus pneumoniae

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 investig...

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Vydáno v:	Respiratory research Ročník 23; číslo 1; s. 1 - 11
Hlavní autoři:	Pereverzeva, Liza, Otto, Natasja A., Roelofs, Joris J. T. H., de Vos, Alex F., van der Poll, Tom
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London BioMed Central 12.09.2022 BioMed Central Ltd Nature Publishing Group BMC
Témata:	Alveolar bone Alveolar macrophages Analysis Bacteria Bone marrow Care and treatment Cell walls Chemokines Cloning Cytokines Diagnosis Encapsulation Experiments Flow cytometry Gene expression Gram-negative bacteria Gram-positive bacteria Histopathology Inflammation Kinases Leukocytes (neutrophilic) Lipopolysaccharides Lipoteichoic acid Liver Liver kinase B1 LKB1 protein Lungs Macrophages Medicine Medicine & Public Health Pathogens Pathology Pneumology/Respiratory System Pneumonia Prevention Respiratory tract infections Risk factors Streptococcal infections Streptococcus infections Streptococcus pneumoniae Tumor necrosis factor-α Tumor suppressor genes Netherlands Basel Switzerland Switzerland Germany Pneumonia Liver kinase B1 Alveolar macrophages Lipoteichoic acid
ISSN:	1465-993X, 1465-9921, 1465-993X
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Popis
Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1465-993X 1465-9921 1465-993X
DOI:	10.1186/s12931-022-02168-6