Differential effect of p47phox and gp91phox deficiency on the course of Pneumococcal Meningitis.

Schaper, Manuela; Leib, Stephen; Meli, Damian N; Brandes, Ralf P; Täuber, Martin G.; Christen, Stephan (2003). Differential effect of p47phox and gp91phox deficiency on the course of Pneumococcal Meningitis. Infection and immunity, 71(7), pp. 4087-4092. American Society for Microbiology 10.1128/IAI.71.7.4087-4092.2003

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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-1 beta, tumor necrosis factor alpha, and matrix metalloproteinase 9 in the cortex. These changes were associated with approximately 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology

UniBE Contributor:

Leib, Stephen; Täuber, Martin G. and Christen, Stephan

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0019-9567

Publisher:

American Society for Microbiology

Language:

English

Submitter:

Stephen Leib

Date Deposited:

01 Sep 2014 08:04

Last Modified:

08 Jul 2015 07:56

Publisher DOI:

10.1128/IAI.71.7.4087-4092.2003

PubMed ID:

12819099

Web of Science ID:

000183797200053

BORIS DOI:

10.7892/boris.52742

URI:

https://boris.unibe.ch/id/eprint/52742 (FactScience: 43470)

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