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Targeting toll-like receptor 7/8 improves host anti-infective response in alcoholic cirrhosis
  1. Emanuele Albano1,
  2. Felix Stickel2
  1. 1Department of Health Sciences and Interdisciplinary Research Centre for Autoimmune Diseases, University of East Piedmont, Novara, Italy
  2. 2Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich, Switzerland
  1. Correspondence to Emanuele Albano, Emanuele Albano, Dept. of Health Sciences, University of East Piedmont, Via Solaroli 17, 28100 Novara, Italy; emanuele.albano{at}med.uniupo.it

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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 (O2) during a process known as oxidative burst. Superoxide anion, in fact, by conversion to hydrogen peroxide, fuels myeloperoxidase-mediated production of the powerful bactericidal agents, hypochlorite and chloramine.5 NOX2 is a multiprotein enzymatic system consisting of the transmembrane proteins gp91phox and p22phox forming the …

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