A lipopolysaccharide-deficient mutant of Neisseria meningitidis elicits attenuated cytokine release by human macrophages and signals via toll-like receptor (TLR) 2 but not via TLR4/MD2
A lipopolysaccharide-deficient mutant of Neisseria meningitidis elicits attenuated cytokine release by human macrophages and signals via toll-like receptor (TLR) 2 but not via TLR4/MD2
Meningococcal disease severity correlates with circulating concentrations of lipopolysaccharide (LPS) and proinflammatory cytokines. Disruption of the lpxA gene of Neisseria meningitidis generated a viable strain that was deficient of detectable LPS. The potency of wild-type N. meningitidis to elicit tumor necrosis factor (TNF)-alpha production by human monocyte-derived macrophages was approximately 10-fold greater than that of the lpxA mutant. Killed wild-type N. meningitidis and its soluble products induced interleukin (IL)-8 and TNF-alpha secretion by transfected HeLa cells expressing Toll-like receptor (TLR) 4/MD2, but the lpxA mutant was inactive via this pathway. In contrast, both strains induced IL-8 promoter activity in TLR2-transfected HeLa cells. These data provide evidence that N. meningitidis contains components other than LPS that can elicit biological responses via pathways that are independent of the TLR4/MD2 receptor system, and TLR2 is one of these alternate pathways. These findings have implications for future therapeutic strategies against meningococcal disease on the basis of the blockade of TLRs and the modulation of LPS activity.
Acyltransferases, Cytokines, Drosophila Proteins, HeLa Cells, Humans, Interleukin-8, Lipopolysaccharide Receptors, Lipopolysaccharides, Macrophages, Membrane Glycoproteins, Mutation, Neisseria meningitidis, Receptors, Cell Surface, Toll-Like Receptor 2, Toll-Like Receptor 4, Toll-Like Receptors, Transfection, Tumor Necrosis Factor-alpha, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
89-96
Pridmore, A.C.
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Wyllie, D.H.
3ec8a490-efb4-4c0a-b2c4-7299b74c61b5
Abdillahi, F.
1888f0ba-d4e3-44b1-88c5-63776b029be0
Steeghs, L.
30bab633-3170-418d-b362-3861f0fd86b4
van der Ley, P
059b2383-eb3e-4def-b545-779ec2c9e3ee
Dower, S.K.
c59b6ed1-57d4-49cb-815c-038a96601ecc
Read, R.C.
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1 January 2001
Pridmore, A.C.
5dd547ac-5dd9-4bec-bffb-8373c57d94a8
Wyllie, D.H.
3ec8a490-efb4-4c0a-b2c4-7299b74c61b5
Abdillahi, F.
1888f0ba-d4e3-44b1-88c5-63776b029be0
Steeghs, L.
30bab633-3170-418d-b362-3861f0fd86b4
van der Ley, P
059b2383-eb3e-4def-b545-779ec2c9e3ee
Dower, S.K.
c59b6ed1-57d4-49cb-815c-038a96601ecc
Read, R.C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Pridmore, A.C., Wyllie, D.H., Abdillahi, F., Steeghs, L., van der Ley, P, Dower, S.K. and Read, R.C.
(2001)
A lipopolysaccharide-deficient mutant of Neisseria meningitidis elicits attenuated cytokine release by human macrophages and signals via toll-like receptor (TLR) 2 but not via TLR4/MD2.
The Journal of Infectious Diseases, 183 (1), .
(doi:10.1086/317647).
Abstract
Meningococcal disease severity correlates with circulating concentrations of lipopolysaccharide (LPS) and proinflammatory cytokines. Disruption of the lpxA gene of Neisseria meningitidis generated a viable strain that was deficient of detectable LPS. The potency of wild-type N. meningitidis to elicit tumor necrosis factor (TNF)-alpha production by human monocyte-derived macrophages was approximately 10-fold greater than that of the lpxA mutant. Killed wild-type N. meningitidis and its soluble products induced interleukin (IL)-8 and TNF-alpha secretion by transfected HeLa cells expressing Toll-like receptor (TLR) 4/MD2, but the lpxA mutant was inactive via this pathway. In contrast, both strains induced IL-8 promoter activity in TLR2-transfected HeLa cells. These data provide evidence that N. meningitidis contains components other than LPS that can elicit biological responses via pathways that are independent of the TLR4/MD2 receptor system, and TLR2 is one of these alternate pathways. These findings have implications for future therapeutic strategies against meningococcal disease on the basis of the blockade of TLRs and the modulation of LPS activity.
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Published date: 1 January 2001
Keywords:
Acyltransferases, Cytokines, Drosophila Proteins, HeLa Cells, Humans, Interleukin-8, Lipopolysaccharide Receptors, Lipopolysaccharides, Macrophages, Membrane Glycoproteins, Mutation, Neisseria meningitidis, Receptors, Cell Surface, Toll-Like Receptor 2, Toll-Like Receptor 4, Toll-Like Receptors, Transfection, Tumor Necrosis Factor-alpha, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
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Local EPrints ID: 416854
URI: http://eprints.soton.ac.uk/id/eprint/416854
ISSN: 0022-1899
PURE UUID: c3886cfa-49c7-4240-a90c-b78fd601599f
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Date deposited: 11 Jan 2018 17:30
Last modified: 16 Mar 2024 04:10
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Author:
A.C. Pridmore
Author:
D.H. Wyllie
Author:
F. Abdillahi
Author:
L. Steeghs
Author:
P van der Ley
Author:
S.K. Dower
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