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Burkholderia cenocepacia induces neutrophil necrosis in chronic granulomatous disease

Journal article
Authors Johan Bylund
P. A. Campsall
R. C. Ma
B. A. Conway
D. P. Speert
Published in J Immunol
Volume 174
Issue 6
Pages 3562-9
Publication year 2005
Published at Institute of Internal Medicine, Dept of Rheumatology and Inflammation Research
Pages 3562-9
Language en
Links www.ncbi.nlm.nih.gov/entrez/query.f...
Keywords Apoptosis, Burkholderia cepacia complex/immunology/*pathogenicity, Case-Control Studies, Female, Granulomatous Disease, Chronic/complications/*immunology/microbiology, Humans, Male, Necrosis, Neutrophils/*immunology/metabolism/pathology, Phagocytosis, Reactive Oxygen Species/metabolism, Virulence
Subject categories Medical and Health Sciences

Abstract

Burkholderia cepacia complex is a life-threatening group of pathogens for patients with chronic granulomatous disease (CGD), whose phagocytes are unable to produce reactive oxygen species (ROS). Unlike other CGD pathogens, B. cepacia complex is particularly virulent, characteristically causing septicemia, and is the bacterial species responsible for most fatalities in these patients. We found that a nonmucoid Burkholderia cenocepacia (a predominant species in the B. cepacia complex) isolate was readily ingested by normal human neutrophils under nonopsonic conditions and promoted apoptosis in these cells. The proapoptotic effect was not due to secreted bacterial products, but was dependent on bacterial viability. Phagocytosis was associated with a robust production of ROS, and the apoptotic neutrophils could be effectively cleared by monocyte-derived macrophages. The proapoptotic effect of B. cenocepacia was independent of ROS production because neutrophils from CGD patients were rendered apoptotic to a similar degree as control cells after challenge. More importantly, neutrophils from CGD patients, but not from normal individuals, were rendered necrotic after phagocytosis of B. cenocepacia. The extreme virulence of B. cepacia complex bacteria in CGD, but not in immunocompetent hosts, could be due to its necrotic potential in the absence of ROS.

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