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Activation of human meningeal cells is modulated by lipopolysaccharide (LPS) and non-LPS components of Toll-like receptor (TLR)4 and TLR2 signalling

Activation of human meningeal cells is modulated by lipopolysaccharide (LPS) and non-LPS components of Toll-like receptor (TLR)4 and TLR2 signalling
Activation of human meningeal cells is modulated by lipopolysaccharide (LPS) and non-LPS components of Toll-like receptor (TLR)4 and TLR2 signalling
The interactions of Neisseria meningitidis with cells of the meninges are critical to progression of the acute, compartmentalized intracranial inflammatory response that is characteristic of meningococcal meningitis. An important virulence mechanism of the bacteria is the ability to shed outer membrane (OM) blebs containing lipopolysaccharide (LPS), which has been assumed to be the major pro-inflammatory molecule produced during meningitis. Comparison of cytokine induction by human meningeal cells following infection with wild-type meningococci, LPS-deficient meningococci or after treatment with OM isolated from both organisms, demonstrated the involvement of non-LPS bacterial components in cell activation. Significantly, recognition of LPS-replete OM did not depend on host cell expression of Toll-like receptor (TLR)4, the accessory protein MD-2 or CD14, or the recruitment of LPS-accessory surface proteins heat shock protein (HSP)70, HSP90?, chemokine receptor CXCR4 and growth differentiation factor (GDF)5. In addition, recognition of LPS-deficient OM was not associated with the expression of TLR2 or any of these other molecules. These data suggest that during meningococcal meningitis innate recognition of both LPS and non-LPS modulins is dependent on the expression of as yet uncharacterized pattern recognition receptors on cells of the meninges. Moreover, the biological consequences of cellular activation by non-LPS modulins suggest that clinical intervention strategies based solely on abrogating the effects of LPS are likely to be only partially effective.
1462-5814
415-430
Humphries, Holly E.
dfbfbf86-71b7-4a11-8192-0afd0eb817a6
Triantafilou, Martha
bb8edb69-5838-45a1-8531-7ae4ba48a768
Makepeace, Benjamin L.
1d886774-1b15-41ed-b6bf-b96f747b1f57
Heckels, John E.
fcfcfafe-5ca8-4728-9c5e-cb67f9af7e31
Triantafilou, Kathy
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Christodoulides, Myron
eba99148-620c-452a-a334-c1a52ba94078
Humphries, Holly E.
dfbfbf86-71b7-4a11-8192-0afd0eb817a6
Triantafilou, Martha
bb8edb69-5838-45a1-8531-7ae4ba48a768
Makepeace, Benjamin L.
1d886774-1b15-41ed-b6bf-b96f747b1f57
Heckels, John E.
fcfcfafe-5ca8-4728-9c5e-cb67f9af7e31
Triantafilou, Kathy
24f4180d-d7b2-43b2-93c7-1c97322f9a50
Christodoulides, Myron
eba99148-620c-452a-a334-c1a52ba94078

Humphries, Holly E., Triantafilou, Martha, Makepeace, Benjamin L., Heckels, John E., Triantafilou, Kathy and Christodoulides, Myron (2005) Activation of human meningeal cells is modulated by lipopolysaccharide (LPS) and non-LPS components of Toll-like receptor (TLR)4 and TLR2 signalling. Cellular Microbiology, 7 (3), 415-430. (doi:10.1111/j.1462-5822.2004.00471.x).

Record type: Article

Abstract

The interactions of Neisseria meningitidis with cells of the meninges are critical to progression of the acute, compartmentalized intracranial inflammatory response that is characteristic of meningococcal meningitis. An important virulence mechanism of the bacteria is the ability to shed outer membrane (OM) blebs containing lipopolysaccharide (LPS), which has been assumed to be the major pro-inflammatory molecule produced during meningitis. Comparison of cytokine induction by human meningeal cells following infection with wild-type meningococci, LPS-deficient meningococci or after treatment with OM isolated from both organisms, demonstrated the involvement of non-LPS bacterial components in cell activation. Significantly, recognition of LPS-replete OM did not depend on host cell expression of Toll-like receptor (TLR)4, the accessory protein MD-2 or CD14, or the recruitment of LPS-accessory surface proteins heat shock protein (HSP)70, HSP90?, chemokine receptor CXCR4 and growth differentiation factor (GDF)5. In addition, recognition of LPS-deficient OM was not associated with the expression of TLR2 or any of these other molecules. These data suggest that during meningococcal meningitis innate recognition of both LPS and non-LPS modulins is dependent on the expression of as yet uncharacterized pattern recognition receptors on cells of the meninges. Moreover, the biological consequences of cellular activation by non-LPS modulins suggest that clinical intervention strategies based solely on abrogating the effects of LPS are likely to be only partially effective.

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Published date: 2005

Identifiers

Local EPrints ID: 27162
URI: http://eprints.soton.ac.uk/id/eprint/27162
ISSN: 1462-5814
PURE UUID: d8cc15f5-2e33-46c7-ae25-631cd7fb56b9
ORCID for Myron Christodoulides: ORCID iD orcid.org/0000-0002-9663-4731

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Date deposited: 26 Apr 2006
Last modified: 16 Mar 2024 02:38

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Contributors

Author: Holly E. Humphries
Author: Martha Triantafilou
Author: Benjamin L. Makepeace
Author: John E. Heckels
Author: Kathy Triantafilou

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