Current Concepts of Hyperinflammation in Chronic Granulomatous Disease

Author:

Rieber Nikolaus12,Hector Andreas12,Kuijpers Taco34,Roos Dirk3,Hartl Dominik12

Affiliation:

1. Children's Hospital, University of Tübingen, 72076 Tübingen, Germany

2. DFG Emmy-Noether Group, Research Center, Children's Hospital, Ludwig-Maximilians-University, 80337 Munich, Germany

3. Sanquin Research Institute, Landsteiner Laboratory, 1006 AD Amsterdam, The Netherlands

4. Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands

Abstract

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.

Publisher

Hindawi Limited

Subject

General Medicine,Immunology,Immunology and Allergy

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