Regulation of oxidative stress by Nrf2 in the pathophysiology of infectious diseases

• Published in: Médecine et maladies infectieuses 2013-03, Vol.43 (3), p.100-107
• Main Authors: Deramaudt, T.B., Dill, C., Bonay, M.
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Antioxidants - pharmacology; Antioxidants - therapeutic use; Antioxydants; Bacterial Infections - immunology; Bacterial Infections - physiopathology; Biological and medical sciences; Communicable Diseases - immunology; Communicable Diseases - physiopathology; Gene Expression Regulation; Host-Pathogen Interactions - immunology; Humans; Immunity, Innate; Infection; Infectious diseases; Intracellular Signaling Peptides and Proteins - physiology; Kelch-Like ECH-Associated Protein 1; Medical sciences; Mice; Molecular Targeted Therapy; Mycobacterium Infections - immunology; Mycobacterium Infections - physiopathology; NF-E2-Related Factor 2 - chemistry; NF-E2-Related Factor 2 - deficiency; NF-E2-Related Factor 2 - physiology; Nrf2; Oxidative stress; Oxidative Stress - genetics; Parasitic Diseases - immunology; Parasitic Diseases - physiopathology; Phagocytosis; Reactive Oxygen Species - metabolism; ROS; Stress oxydant; Transcription, Genetic; Virus Diseases - immunology; Virus Diseases - physiopathology
• ISSN: 0399-077X; 1769-6690
• DOI: 10.1016/j.medmal.2013.02.004

The innate immune system, including phagocytic cells, is the first line of defense against pathogens. During infection by microorganisms such as viruses, bacteria, or parasites, phagocytic cells produce an excess of oxidants, a crucial process for the clearance of pathogens. This increase in oxidants creates an imbalance between oxidants and endogenous antioxidants. Left unchecked, this acute or chronic oxidative stress can lead to apoptotic cell-death and oxidative stress-induced diseases including neurodegenerative and cardiovascular disorders, premature aging, secondary infections, and cancer. The activation of nuclear factor E2-related factor 2 (Nrf2) is an efficient antioxidant defensive mechanism used by host cells to counteract oxidative stress. The transcription factor Nrf2 has been identified as the master regulator of several hundred of genes involved in the antioxidant defense response. The review objectives were to collect recent findings on the contribution of oxidative stress to complications of infection, and to highlight the beneficial impact of antioxidants in reducing inflammation and oxidant-related tissue damage. Furthermore, a direct relationship between infection and decline in Nrf2 activity has been demonstrated. Thus, an interesting therapeutic approach in disease prevention and treatment of stress-related diseases may consist in optimizing antibiotic or antiviral therapy with a combination of Nrf2 inducer treatment. Le système immunitaire inné, composé de cellules phagocytaires, est la première ligne de défense contre l’infection par des agents pathogènes. Lors d’infections par les microorganismes tels que les virus, les bactéries ou les parasites, les cellules phagocytaires produisent en excès des agents oxydants. Ce déséquilibre entre oxydants et antioxydants endogènes est un processus crucial dans l’élimination des pathogènes. En absence de contrôle, ce stress oxydant aigu ou chronique peut mener à la mort cellulaire programmée, ou apoptose, et au développement de maladies telles que les troubles neurodégénératifs et cardiovasculaires, le vieillissement prématuré, les infections secondaires et le cancer. Un mécanisme antioxydant efficace, utilisé par les cellules pour combattre le stress oxydant, consiste à activer le facteur de transcription nuclear factor E2-related factor 2 ou Nrf2. Nrf2 est le coordinateur de plusieurs centaines de gènes impliqués dans la réponse antioxydante. Cette revue vise à réunir les études récentes su