Role of Liver Kinase 1B in Platelet Activation and Host Defense During Klebsiella pneumoniae-Induced Pneumosepsis

Pneumonia is the most common cause of sepsis, with Klebsiella pneumoniae frequently implicated as a causative pathogen. Platelets play a crucial role in host defense during sepsis, and their activation is essential for effective immune responses, which is at least in part induced through activation...

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Vydáno v:	International journal of molecular sciences Ročník 26; číslo 8; s. 3714
Hlavní autoři:	Chouchane, Osoul, Léopold, Valentine, van Linge, Christine C. A., de Vos, Alex F., Roelofs, Joris J. T. H., van ‘t Veer, Cornelis, van der Poll, Tom
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Switzerland MDPI AG 14.04.2025 MDPI
Témata:	AMP-Activated Protein Kinases Animals Bacterial pneumonia Blood platelets Blood Platelets - metabolism Collagen Cytokines Enzymes Ethylenediaminetetraacetic acid Immune response Infections Kinases Klebsiella Infections - immunology Klebsiella Infections - metabolism Klebsiella Infections - microbiology Klebsiella pneumoniae - pathogenicity Medical research Medicine, Experimental Metabolism Mice Mice, Inbred C57BL Mice, Knockout Pathogens Physiological aspects Platelet Activation Platelet Membrane Glycoproteins - metabolism Pneumonia Protein Serine-Threonine Kinases - genetics Protein Serine-Threonine Kinases - metabolism Sepsis Sepsis - immunology Sepsis - microbiology Thrombin United States Netherlands California microbial infection microbes–host interaction molecular and cell biology
ISSN:	1422-0067, 1661-6596, 1422-0067
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Shrnutí:	Pneumonia is the most common cause of sepsis, with Klebsiella pneumoniae frequently implicated as a causative pathogen. Platelets play a crucial role in host defense during sepsis, and their activation is essential for effective immune responses, which is at least in part induced through activation of the collagen receptor glycoprotein (GP)VI. Platelets require energy for their activation, and Liver kinase B1 (LKB1) is a key regulator of energy metabolism. We sought to determine the role of LKB1 in platelet function and host response during K. pneumoniae-induced pneumosepsis. Platelet-specific-Lkb1-deficient mice were generated and compared to control littermates. Platelet counts were unaffected by Lkb1 deficiency in naïve mice. However, Lkb1-deficient platelets exhibited significant hyperreactivity to GPVI stimulation, an effect not observed after stimulation of the thrombin receptor protease-activated receptor 4. During K. pneumoniae infection, platelets of both Lkb1-deficient and control mice became equally hyporesponsive to GPVI stimulation, without differences between genotypes. Platelet-specific Lkb1 deficiency did not alter bacterial outgrowth or dissemination, inflammatory responses, or lung pathology. These findings suggest that while Lkb1 plays a role in regulating platelet activation in response to GPVI stimulation, it does not significantly impact platelet activation or the host response during pneumonia-induced sepsis.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1422-0067 1661-6596 1422-0067
DOI:	10.3390/ijms26083714