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Infection and Immunity, July 2003, p. 4087-4092, Vol. 71, No. 7
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.7.4087-4092.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Differential Effect of p47phox and gp91phox Deficiency on the Course of Pneumococcal Meningitis

Manuela Schaper,1 Stephen L. Leib,1 Damian N. Meli,1 Ralf P. Brandes,2 Martin G. Täuber,1 and Stephan Christen1*

Institute for Infectious Diseases, University of Berne, 3010 Berne, Switzerland,1 Institute for Cardiovascular Physiology, Johann Wolfgang Goethe University, 60590 Frankfurt/Main, Germany2

Received 5 December 2002/ Returned for modification 21 January 2003/ Accepted 3 March 2003

Bacterial meningitis is a severe inflammatory disease of the central nervous system and is characterized by massive infiltration of granulocytes into the cerebrospinal fluid (CSF). To assess the role of NADPH oxidase-derived reactive oxygen species (ROS) in pneumococcal meningitis, mice deficient in either the gp91 subunit (essential for functioning of the phagocyte enzyme) or the p47 subunit (essential for functioning of homologous enzymes in nonphagocytic cells) were intracisternally infected with live Streptococcus pneumoniae, and defined disease parameters were measured during the acute stage of infection. While none of the parameters measured (including CSF bacterial titers) were significantly different in gp91-/- and wild-type mice, the infection in p47-/- mice was associated with significantly increased inflammation of the subarachnoid and ventricular space, disruption of the blood-brain barrier, and the presence of interleukin-1ß, tumor necrosis factor alpha, and matrix metalloproteinase 9 in the cortex. These changes were associated with ~10-fold-higher CSF bacterial titers in p47-/- mice than in wild-type mice (P < 0.001). In contrast to infection with live bacteria, the inflammatory response, including CSF leukocytosis, was significantly attenuated in p47-/- mice (but not gp91-/- mice) challenged with a fixed number of heat-inactivated pneumococci. Impairment of the host defense appeared to be responsible for the higher bacterial titers in p47-/- mice. Therefore, these results indicate that ROS generated by a gp91-independent NADPH oxidase(s) are important for establishing an adequate inflammatory response to pneumococcal CSF infection.

* Corresponding author. Mailing address: Institute for Infectious Diseases, University of Berne, Friedbuehlstrasse 51, CH-3010 Berne, Switzerland. Phone: 41 (31) 632 8707. Fax: 41 (31) 632 3550. E-mail: stephan.christen{at}ifik.unibe.ch.

Editor: F. C. Fang

Infection and Immunity, July 2003, p. 4087-4092, Vol. 71, No. 7
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.7.4087-4092.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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