Brain Advance Access published online on August 5, 2006
Brain, doi:10.1093/brain/awl192
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1 Clinical Immunology, University Hospital Zurich, Zurich, Switzerland
* To whom correspondence should be addressed. 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-1
Received January 24, 2006
Revised June 1, 2006
Accepted June 1, 2006
Article
TGF
Ursula Malipiero 1 *, Uwe Koedel 2 *, Hans-Walter Pfister 2, Per Levéen 3, Kurt Bürki 4, Walter Reith 5, and Adriano Fontana 1 *
receptor II gene deletion in leucocytes prevents cerebral vasculitis in bacterial meningitis
2 Department of Neurology, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany
3 Department of Molecular Medicine and Gene Therapy, Lund University, Lund, Sweden
4 Institute of Laboratory Animal Science, University of Zurich, Zurich, Switzerland
5 Department of Pathology and Immunology, Centre Médicale Universitaire (CMU), Geneva, Switzerland
Adriano Fontana, E-mail: adriano.fontana{at}usz.ch
Abstract 
(IL-1). Although these immune factors assist in clearance of bacteria, they also result in neuronal injury associated with meningitis. Transforming growth factor beta (TGF) is a potent deactivator of PMN and macrophages since TGF suppresses the production of ROI, RNI and IL-1. Here, we report that the deletion of the TGF 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 TGF receptor II were not explained by altered expression of chemokines acting on PMN. Instead, TGF was found to impair the expression of L (leucocyte)-selectin on PMN from control mice but not from mice lacking TGF receptor II. L-Selectin is known to be essential for PMN recruitment in bacterial meningitis. We conclude that defective TGF signalling in PMN is beneficial in bacterial meningitis by ameliorating migration of PMN and bacterial clearance.
*These two authors have contributed equally to this work.
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