Neutrophils and galectin-3 defend mice from lethal bacterial infection and humans from acute respiratory failure.
Sudipta DasTomasz W KaminskiBrent T SchlegelWilliam G BainSanmei HuAkruti PatelSagar L KaleKong ChenJanet S LeeRama K MallampalliValerian E KaganDhivyaa RajasundaramBryan J McVerryPrithu SunddGeorgios D KitsiosAnuradha RayPrabir RayPublished in: Nature communications (2024)
Respiratory infection by Pseudomonas aeruginosa, common in hospitalized immunocompromised and immunocompetent ventilated patients, can be life-threatening because of antibiotic resistance. This raises the question of whether the host's immune system can be educated to combat this bacterium. Here we show that prior exposure to a single low dose of lipopolysaccharide (LPS) protects mice from a lethal infection by P. aeruginosa. LPS exposure trained the innate immune system by promoting expansion of neutrophil and interstitial macrophage populations distinguishable from other immune cells with enrichment of gene sets for phagocytosis- and cell-killing-associated genes. The cell-killing gene set in the neutrophil population uniquely expressed Lgals3, which encodes the multifunctional antibacterial protein, galectin-3. Intravital imaging for bacterial phagocytosis, assessment of bacterial killing and neutrophil-associated galectin-3 protein levels together with use of galectin-3-deficient mice collectively highlight neutrophils and galectin-3 as central players in LPS-mediated protection. Patients with acute respiratory failure revealed significantly higher galectin-3 levels in endotracheal aspirates (ETAs) of survivors compared to non-survivors, galectin-3 levels strongly correlating with a neutrophil signature in the ETAs and a prognostically favorable hypoinflammatory plasma biomarker subphenotype. Taken together, our study provides impetus for harnessing the potential of galectin-3-expressing neutrophils to protect from lethal infections and respiratory failure.
Keyphrases
- respiratory failure
- extracorporeal membrane oxygenation
- mechanical ventilation
- low dose
- inflammatory response
- pseudomonas aeruginosa
- acute respiratory distress syndrome
- single cell
- end stage renal disease
- genome wide
- intensive care unit
- immune response
- chronic kidney disease
- young adults
- high dose
- adipose tissue
- cystic fibrosis
- skeletal muscle
- gene expression
- stem cells
- mesenchymal stem cells
- newly diagnosed
- mass spectrometry
- metabolic syndrome
- prognostic factors
- liver failure
- photodynamic therapy
- machine learning
- patient reported outcomes
- binding protein
- bioinformatics analysis
- climate change
- aortic dissection
- bone marrow
- patient reported
- cancer therapy
- multidrug resistant