Airway immunometabolites fuel Pseudomonas aeruginosa infection.
Pulmonary infections are associated with a brisk inflammatory reaction to bacterial surface components. Lipopolysaccharides (LPS) trigger macrophage activation and release of mitochondrial metabolites that control the intensity of the immune response. Whereas succinate induces oxidative stress (ROS), HIF1α stabilization, glycolysis and IL-1β release, itaconate suppresses inflammation by inhibiting succinate oxidation, glycolytic flux and promoting anti-oxidant Nrf2-HO-1 functions. P. aeruginosa is a major pathogen associated with acute and chronic lung infection. Although both secreted toxins, LPS and proteases are key factors to establish acute P. aeruginosa pneumonia, lack of these components in chronic P. aeruginosa isolates suggest these organisms exploit other mechanisms to adapt and persist in the lung. Upon inhalation, P. aeruginosa strains trigger airway macrophage reprograming and bacterial variants obtained from acutely and chronically infected subjects exhibit metabolic adaptation consistent with succinate and itaconate assimilation; namely, high expression of extracellular polysaccharides (EPS), reduced lptD-LPS function, increased glyoxylate shunt (GS) activity and substantial biofilm production. In this review we discuss recent findings illustrating how P. aeruginosa induces and adapts to macrophage metabolites in the human lung, and that catabolism of succinate and itaconate contribute to their formidable abilities to tolerate oxidative stress, phagocytosis and immune clearance.
['Riquelme|Sebastián A|SA|', 'Prince|Alice|A|']
D000818:Animals D018441:Biofilms D004734:Energy Metabolism D054884:Host-Pathogen Interactions D006801:Humans D018836:Inflammation Mediators D008168:Lung D008262:Macrophage Activation D016676:Macrophages, Alveolar D018384:Oxidative Stress D018410:Pneumonia, Bacterial D011552:Pseudomonas Infections D011550:Pseudomonas aeruginosa D017382:Reactive Oxygen Species
Pseudomonas aeruginosa Succinate ROS Itaconate Pneumonia Adaptation Biofilm Cystic fibrosis Immunometabolism Metabolic stress