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Infection and Immunity, March 2009, p. 1015-1021, Vol. 77, No. 3
0019-9567/09/$08.00+0     doi:10.1128/IAI.01029-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Role of NADPH Phagocyte Oxidase in Host Defense against Acute Respiratory Acinetobacter baumannii Infection in Mice{triangledown}

Hongyu Qiu, Rhonda KuoLee, Greg Harris, and Wangxue Chen*

Institute for Biological Sciences, National Research Council Canada, 100 Sussex Drive, Ottawa, Ontario K1A 0R6, Canada

Received 18 August 2008/ Returned for modification 8 October 2008/ Accepted 8 December 2008

Acinetobacter baumannii is an emerging bacterial pathogen that rapidly develops multiple-drug resistance and is responsible for many nosocomial pulmonary infections. This study investigated the role of the NADPH phagocyte oxidase (phox) and inducible nitric oxide synthase (NOS2) in the host defense against respiratory infection with A. baumannii in mouse models of intranasal A. baumannii infection. gp91phox–/– mice showed higher susceptibility to A. baumannii infection than wild-type (WT) C57BL/6 mice, with significantly greater bacterial counts in their lungs (1,000-fold) (P < 0.005) and spleens (10-fold) (P < 0.05). Moreover, all of the gp91phox–/– mice succumbed to infection within 48 h. In contrast, only a moderate increase in bacterial burdens was detected in the lungs of NOS2–/– mice, and all NOS2–/– mice survived infection. Compared to WT mice, the pulmonary influx of inflammatory cells and serum and local inflammatory cytokine/chemokine responses were not obviously impaired at 4 h and were significantly higher at 24 h (P < 0.05) in gp91phox–/– mice, but NADPH-deficient neutrophils were unable to control bacterial replication and extrapulmonary dissemination. Thus, NADPH phagocyte oxidase appears to play a crucial role in the neutrophil-mediated host defense against A. baumannii.


* Corresponding author. Mailing address: Institute for Biological Sciences, National Research Council Canada, 100 Sussex Drive, Ottawa, Ontario K1A 0R6, Canada. Phone: (613) 991-0924. Fax: (613) 952-9092. E-mail: wangxue.chen{at}nrc.gc.ca

{triangledown} Published ahead of print on 22 December 2008.

Editor: B. A. McCormick


Infection and Immunity, March 2009, p. 1015-1021, Vol. 77, No. 3
0019-9567/09/$08.00+0     doi:10.1128/IAI.01029-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.