Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

TGF beta receptor II gene deletion in leucocytes prevents cerebral vasculitis in bacterial meningitis

Malipiero, Ursula ; Koedel, Uwe ; Pfister, Hans-Walter ; Levéen, Per LU ; Buerki, Kurt ; Reith, Walter and Fontana, Adriano (2006) In Brain 129. p.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-1 beta (IL-1 beta). Although these immune factors assist in clearance of bacteria, they also result in neuronal injury associated with meningitis. Transforming growth factor beta (TGF beta) is a potent deactivator of PMN and macrophages since TGF beta suppresses the production of ROI, RNI and IL-1. Here, we report that the deletion of the TGF beta receptor II gene in PMN enhances PMN recruitment into the CNS of mice with Streptococcus pneumoniae meningitis. This was associated with more... (More)
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 beta (IL-1 beta). Although these immune factors assist in clearance of bacteria, they also result in neuronal injury associated with meningitis. Transforming growth factor beta (TGF beta) is a potent deactivator of PMN and macrophages since TGF beta suppresses the production of ROI, RNI and IL-1. Here, we report that the deletion of the TGF beta 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 beta receptor II were not explained by altered expression of chemokines acting on PMN. Instead, TGF beta was found to impair the expression of L (leucocyte)-selectin on PMN from control mice but not from mice lacking TGF beta receptor II. L-Selectin is known to be essential for PMN recruitment in bacterial meningitis. We conclude that defective TGF beta signalling in PMN is beneficial in bacterial meningitis by ameliorating migration of PMN and bacterial clearance. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
blood brain barrier, neuronal injury, innate immunity, stroke, chemokines
in
Brain
volume
129
pages
2404 - 2415
publisher
Oxford University Press
external identifiers
  • wos:000240679700016
  • pmid:16891635
  • scopus:33749266512
ISSN
1460-2156
DOI
10.1093/brain/awl192
language
English
LU publication?
yes
id
935411e0-349e-492f-98f5-9970a58485ac (old id 392805)
date added to LUP
2016-04-01 12:23:47
date last changed
2022-01-27 03:10:52
@article{935411e0-349e-492f-98f5-9970a58485ac,
  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-1 beta (IL-1 beta). Although these immune factors assist in clearance of bacteria, they also result in neuronal injury associated with meningitis. Transforming growth factor beta (TGF beta) is a potent deactivator of PMN and macrophages since TGF beta suppresses the production of ROI, RNI and IL-1. Here, we report that the deletion of the TGF beta 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 beta receptor II were not explained by altered expression of chemokines acting on PMN. Instead, TGF beta was found to impair the expression of L (leucocyte)-selectin on PMN from control mice but not from mice lacking TGF beta receptor II. L-Selectin is known to be essential for PMN recruitment in bacterial meningitis. We conclude that defective TGF beta signalling in PMN is beneficial in bacterial meningitis by ameliorating migration of PMN and bacterial clearance.}},
  author       = {{Malipiero, Ursula and Koedel, Uwe and Pfister, Hans-Walter and Levéen, Per and Buerki, Kurt and Reith, Walter and Fontana, Adriano}},
  issn         = {{1460-2156}},
  keywords     = {{blood brain barrier; neuronal injury; innate immunity; stroke; chemokines}},
  language     = {{eng}},
  pages        = {{2404--2415}},
  publisher    = {{Oxford University Press}},
  series       = {{Brain}},
  title        = {{TGF beta receptor II gene deletion in leucocytes prevents cerebral vasculitis in bacterial meningitis}},
  url          = {{http://dx.doi.org/10.1093/brain/awl192}},
  doi          = {{10.1093/brain/awl192}},
  volume       = {{129}},
  year         = {{2006}},
}