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Current Concepts of Hyperinflammation in Chronic Granulomatous Disease
Chronic granulomatous disease (CGD) is the most common inherited disorder of phagocytic functions, caused by genetic defects in the leukocyte nicotinamide dinucleotide phosphate (NADPH) oxidase. Consequently, CGD phagocytes are impaired in destroying phagocytosed microorganisms, rendering the patien...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3144705/ https://www.ncbi.nlm.nih.gov/pubmed/21808651 http://dx.doi.org/10.1155/2012/252460 |
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author | Rieber, Nikolaus Hector, Andreas Kuijpers, Taco Roos, Dirk Hartl, Dominik |
author_facet | Rieber, Nikolaus Hector, Andreas Kuijpers, Taco Roos, Dirk Hartl, Dominik |
author_sort | Rieber, Nikolaus |
collection | PubMed |
description | Chronic granulomatous disease (CGD) is the most common inherited disorder of phagocytic functions, caused by genetic defects in the leukocyte nicotinamide dinucleotide phosphate (NADPH) oxidase. Consequently, CGD phagocytes are impaired in destroying phagocytosed microorganisms, rendering the patients susceptible to bacterial and fungal infections. Besides this immunodeficiency, CGD patients suffer from various autoinflammatory symptoms, such as granuloma formation in the skin or urinary tract and Crohn-like colitis. Owing to improved antimicrobial treatment strategies, the majority of CGD patients reaches adulthood, yet the autoinflammatory manifestations become more prominent by lack of causative treatment options. The underlying pathomechanisms driving hyperinflammatory reactions in CGD are poorly understood, but recent studies implicate reduced neutrophil apoptosis and efferocytosis, dysbalanced innate immune receptors, altered T-cell surface redox levels, induction of Th17 cells, the enzyme indolamine-2,3-dioxygenase (IDO), impaired Nrf2 activity, and inflammasome activation. Here we discuss immunological mechanisms of hyperinflammation and their potential therapeutic implications in CGD. |
format | Online Article Text |
id | pubmed-3144705 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-31447052011-08-01 Current Concepts of Hyperinflammation in Chronic Granulomatous Disease Rieber, Nikolaus Hector, Andreas Kuijpers, Taco Roos, Dirk Hartl, Dominik Clin Dev Immunol Review Article Chronic granulomatous disease (CGD) is the most common inherited disorder of phagocytic functions, caused by genetic defects in the leukocyte nicotinamide dinucleotide phosphate (NADPH) oxidase. Consequently, CGD phagocytes are impaired in destroying phagocytosed microorganisms, rendering the patients susceptible to bacterial and fungal infections. Besides this immunodeficiency, CGD patients suffer from various autoinflammatory symptoms, such as granuloma formation in the skin or urinary tract and Crohn-like colitis. Owing to improved antimicrobial treatment strategies, the majority of CGD patients reaches adulthood, yet the autoinflammatory manifestations become more prominent by lack of causative treatment options. The underlying pathomechanisms driving hyperinflammatory reactions in CGD are poorly understood, but recent studies implicate reduced neutrophil apoptosis and efferocytosis, dysbalanced innate immune receptors, altered T-cell surface redox levels, induction of Th17 cells, the enzyme indolamine-2,3-dioxygenase (IDO), impaired Nrf2 activity, and inflammasome activation. Here we discuss immunological mechanisms of hyperinflammation and their potential therapeutic implications in CGD. Hindawi Publishing Corporation 2012 2011-07-25 /pmc/articles/PMC3144705/ /pubmed/21808651 http://dx.doi.org/10.1155/2012/252460 Text en Copyright © 2012 Nikolaus Rieber et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Article Rieber, Nikolaus Hector, Andreas Kuijpers, Taco Roos, Dirk Hartl, Dominik Current Concepts of Hyperinflammation in Chronic Granulomatous Disease |
title | Current Concepts of Hyperinflammation in Chronic Granulomatous Disease |
title_full | Current Concepts of Hyperinflammation in Chronic Granulomatous Disease |
title_fullStr | Current Concepts of Hyperinflammation in Chronic Granulomatous Disease |
title_full_unstemmed | Current Concepts of Hyperinflammation in Chronic Granulomatous Disease |
title_short | Current Concepts of Hyperinflammation in Chronic Granulomatous Disease |
title_sort | current concepts of hyperinflammation in chronic granulomatous disease |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3144705/ https://www.ncbi.nlm.nih.gov/pubmed/21808651 http://dx.doi.org/10.1155/2012/252460 |
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