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

Content Provider	PubMed Central
Author	Schaper, Manuela Leib, Stephen L. Meli, Damian N. Brandes, Ralf P. Täuber, Martin G. Christen, Stephan
Copyright Year	2003
Abstract	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-1β, 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.
Related Links	http://dx.doi.org/10.1128/iai.71.7.4087-4092.2003
Ending Page	4092
Page Count	6
Starting Page	4087
File Format	PDF
ISSN	00199567
e-ISSN	10985522
Journal	Infection and Immunity
Issue Number	7
Volume Number	71
Language	English
Publisher	American Society for Microbiology
Publisher Date	2003-07-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Immunology Microbiology Parasitology Infectious Diseases Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Parasitology Immunology Microbiology

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