Targeting toll-like receptor 7/8 improves host anti-infective response in alcoholic cirrhosis

The production of reactive oxygen species (ROS) by activated macrophages and neutrophil granulocytes represents an important cause of alcohol-induced oxidative stress and significantly contributes to the pathogenesis of alcoholic liver disease (ALD).1 Furthermore, diffuse neutrophil infiltration of the liver is a key feature of acute alcoholic hepatitis actively participating to parenchymal injury.2 However, during ALD progression to cirrhosis, neutrophil functions such as ROS production, bacterial phagocytosis and granule exocytosis are impaired leading to an increased susceptibility to bacterial infections of cirrhotic patients.3 Indeed, the development of bacterial peritonitis is a common complication of cirrhosis, while sepsis is a major cause of mortality in  patients with decompensated alcoholic cirrhosis being also associated with multiorgan failure and immune deficiencies.4

The key role of neutrophils in antibacterial defences mainly relies on the capacity of the enzyme NADPH oxidase 2 (NOX2) to generate superoxide anion...

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