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TGFbeta receptor II gene deletion in leucocytes prevents cerebral vasculitis in bacterial meningitis

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.

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.

Additional indexing

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

04 Faculty of Medicine > University Hospital Zurich > Clinic for Immunology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Health Sciences > Neurology (clinical)
Language:English
Date:5 August 2006
Deposited On:25 Mar 2009 10:34
Last Modified:17 Jul 2025 12:49
Publisher:Oxford University Press
ISSN:0006-8950
OA Status:Hybrid
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/brain/awl192
PubMed ID:16891635
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