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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-10881

Malipiero, U; Koedel, U; Pfister, H W; Levéen, P; Bürki, K; Reith, W; Fontana, A (2006). TGFbeta receptor II gene deletion in leucocytes prevents cerebral vasculitis in bacterial meningitis. Brain : a journal of neurology, 129(9):2404-2415.

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Abstract

In bacterial meningitis, chemokines lead to recruitment of polymorphonuclear leucocytes (PMN) into the CNS. At the site of infection in the subarachnoid space, PMN release reactive oxygen species, reactive nitrogen intermediates (RNI) and interleukin-1beta (IL-1beta). Although these immune factors assist in clearance of bacteria, they also result in neuronal injury associated with meningitis. Transforming growth factor beta (TGFbeta) is a potent deactivator of PMN and macrophages since TGFbeta suppresses the production of ROI, RNI and IL-1. Here, we report that the deletion of the TGFbeta receptor II gene in PMN enhances PMN recruitment into the CNS of mice with Streptococcus pneumoniae meningitis. This was associated with more efficient clearance of bacteria, and almost complete prevention of intracerebral necrotizing vasculitis. Differences in PMN in the CNS of infected control mice and mice lacking TGFbeta receptor II were not explained by altered expression of chemokines acting on PMN. Instead, TGFbeta was found to impair the expression of L (leucocyte)-selectin on PMN from control mice but not from mice lacking TGFbeta receptor II. L-selectin is known to be essential for PMN recruitment in bacterial meningitis. We conclude that defective TGFbeta signalling in PMN is beneficial in bacterial meningitis by ameliorating migration of PMN and bacterial clearance.

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17 citations in Web of Science®
19 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Laboratory Animal Science
04 Faculty of Medicine > Institute of Laboratory Animal Science

04 Faculty of Medicine > University Hospital Zurich > Clinic for Immunology
DDC:570 Life sciences; biology
610 Medicine & health
Date:5 August 2006
Deposited On:25 Mar 2009 10:34
Last Modified:27 Nov 2013 23:18
Publisher:UNSPECIFIED
ISSN:1460-2156
Additional Information:This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Brain following peer review. The definitive publisher-authenticated version Brain 2006 129(9):2404-2415; doi:10.1093/brain/awl192 is available online at: http://brain.oxfordjournals.org
Publisher DOI:10.1093/brain/awl192
PubMed ID:16891635

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