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

Abstract

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.

• Authors: T B Deramaudt, C Dill, M Bonay
• Journal: Medecine et maladies infectieuses (Med Mal Infect) Vol. 43 Issue 3 Pg. 100-7 (Mar 2013) ISSN: 1769-6690 [Electronic] France
• PMID: 23499316 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antioxidants
• Intracellular Signaling Peptides and Proteins
• KEAP1 protein, human
• Kelch-Like ECH-Associated Protein 1
• NF-E2-Related Factor 2
• NFE2L2 protein, human
• Nfe2l2 protein, mouse
• Reactive Oxygen Species

Topics

• Animals
• Antioxidants (pharmacology, therapeutic use)
• Bacterial Infections (immunology, physiopathology)
• Communicable Diseases (immunology, physiopathology)
• Gene Expression Regulation
• Host-Pathogen Interactions (immunology)
• Humans
• Immunity, Innate
• Intracellular Signaling Peptides and Proteins (physiology)
• Kelch-Like ECH-Associated Protein 1
• Mice
• Molecular Targeted Therapy
• Mycobacterium Infections (immunology, physiopathology)
• NF-E2-Related Factor 2 (chemistry, deficiency, physiology)
• Oxidative Stress (genetics)
• Parasitic Diseases (immunology, physiopathology)
• Phagocytosis
• Reactive Oxygen Species (metabolism)
• Transcription, Genetic
• Virus Diseases (immunology, physiopathology)