Diet-induced obesity in mice impairs host defense against Klebsiella pneumonia in vivo and glucose transport and bactericidal functions in neutrophils in vitro
| Autor: | Jeffrey L. Curtis, Peter Mancuso, Benjamin Bouchard, Kanakadurga Singer, Dave Bridges, Christine M. Freeman, Anne M. Weitzel, Cameron Griffin |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Blood Glucose
Male Neutrophils Physiology Adipose tissue Leukocyte Count Bone Marrow Lung Adiposity Glucose Transporter Type 1 Glucose Transporter Type 3 biology Klebsiella pneumoniae medicine.anatomical_structure Host-Pathogen Interactions Cytokines Bronchoalveolar Lavage Fluid Glycolysis Research Article Pulmonary and Respiratory Medicine medicine.medical_specialty Adipose Tissue White Phagocytosis Deoxyglucose Diet High-Fat In vivo Physiology (medical) Internal medicine medicine Animals Obesity RNA Messenger Body Weight Glucose transporter Biological Transport Pneumonia Cell Biology medicine.disease Bacterial Load Diet Klebsiella Infections Mice Inbred C57BL Glucose Endocrinology biology.protein GLUT1 Klebsiella pneumonia Spleen GLUT3 |
| Zdroj: | Am J Physiol Lung Cell Mol Physiol |
| ISSN: | 1522-1504 1040-0605 |
| Popis: | Obesity impairs host defense against Klebsiella pneumoniae, but responsible mechanisms are incompletely understood. To determine the impact of diet-induced obesity on pulmonary host defense against K. pneumoniae, we fed 6-wk-old male C57BL/6j mice a normal diet (ND) or high-fat diet (HFD) (13% vs. 60% fat, respectively) for 16 wk. Mice were intratracheally infected with Klebsiella, assayed at 24 or 48 h for bacterial colony-forming units, lung cytokines, and leukocytes from alveolar spaces, lung parenchyma, and gonadal adipose tissue were assessed using flow cytometry. Neutrophils from uninfected mice were cultured with and without 2-deoxy-d-glucose (2-DG) and assessed for phagocytosis, killing, reactive oxygen intermediates (ROI), transport of 2-DG, and glucose transporter (GLUT1–4) transcripts, and protein expression of GLUT1 and GLUT3. HFD mice had higher lung and splenic bacterial burdens. In HFD mice, baseline lung homogenate concentrations of IL-1β, IL-6, IL-17, IFN-γ, CXCL2, and TNF-α were reduced relative to ND mice, but following infection were greater for IL-6, CCL2, CXCL2, and IL-1β (24 h only). Despite equivalent lung homogenate leukocytes, HFD mice had fewer intraalveolar neutrophils. HFD neutrophils exhibited decreased Klebsiella phagocytosis and killing and reduced ROI to heat-killed Klebsiella in vitro. 2-DG transport was lower in HFD neutrophils, with reduced GLUT1 and GLUT3 transcripts and protein (GLUT3 only). Blocking glycolysis with 2-DG impaired bacterial killing and ROI production in neutrophils from mice fed ND but not HFD. Diet-induced obesity impairs pulmonary Klebsiella clearance and augments blood dissemination by reducing neutrophil killing and ROI due to impaired glucose transport. |
| Databáze: | OpenAIRE |
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