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Blood, 24 September 2009, Vol. 114, No. 13, pp. 2619-2622. Prepublished online as a Blood First Edition Paper on June 18, 2009July 9, 2009; DOI 10.1182/blood-2009-05-221606. This Article Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2009-05-221606v1 blood-2009-05-221606v2 114/13/2619    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Bianchi, M. Articles by Reichenbach, J. PubMed PubMed Citation Articles by Bianchi, M. Articles by Reichenbach, J. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 12, 2009 Accepted June 8, 2009 Restoration of NET formation by gene therapy in CGD controls aspergillosis Matteo Bianchi, Abdul Hakkim, Volker Brinkmann, Ulrich Siler, Reinhard A. Seger, Arturo Zychlinsky, and Janine Reichenbach* Division of Immunology/Haematology/BMT, University Children's Hospital Zurich, Zurich, Switzerland Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany Microscopy Core Facility, Max Planck Institute for Infection Biology, Berlin, Germany * Corresponding author; email: janine.reichenbach{at}kispi.uzh.ch. Chronic granulomatous disease (CGD) patients have impaired NADPH oxidase function, resulting in poor antimicrobial activity of neutrophils including the inability to generate Neutrophil Extracellular Traps (NETs). Invasive aspergillosis is the leading cause of death in patients with CGD; it is unclear how neutrophils control Aspergillus species in healthy individuals. The aim of this study was to determine whether gene therapy (GT) restores NET formation in CGD by complementation of NADPH oxidase function, and whether NETs have antimicrobial activity against Aspergillus nidulans. Here we show that reconstitution of NET formation by GT in a patient with CGD restores neutrophil elimination of Aspergillus nidulans conidia and hyphae and is associated with rapid cure of pre-existing therapy refractory invasive pulmonary aspergillosis, underlining the role of functional NADPH oxidase in NET formation and antifungal activity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: Reconstitution of protection against Aspergillus infection in chronic granulomatous disease (CGD) Quinten Remijsen, Peter Vandenabeele, Jean Willems, and Taco W. Kuijpers Blood 2009 114: 3497. [Full Text] [PDF] Response: Protecting against Aspergillus infection in CGD Abdul Hakkim, Robert Hurwitz, Matteo Bianchi, Volker Brinkmann, Ulrich Siler, Reinhard A. Seger, Arturo Zychlinsky, and Janine Reichenbach Blood 2009 114: 3498. [Full Text] [PDF] This article has been cited by other articles: Q. Remijsen, P. Vandenabeele, J. Willems, and T. W. Kuijpers Reconstitution of protection against Aspergillus infection in chronic granulomatous disease (CGD) Blood, October 15, 2009; 114(16): 3497 - 3497. [Full Text] [PDF] A. Hakkim, R. Hurwitz, M. Bianchi, V. Brinkmann, U. Siler, R. A. Seger, A. Zychlinsky, and J. Reichenbach Response: Protecting against Aspergillus infection in CGD Blood, October 15, 2009; 114(16): 3498 - 3498. [Full Text] [PDF]

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