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Activation of toll-like receptor 2 (TLR2) and TLR4/MD2 by Neisseria is independent of capsule and lipooligosaccharide (LOS) sialylation but varies widely among LOS from different strains

Activation of toll-like receptor 2 (TLR2) and TLR4/MD2 by Neisseria is independent of capsule and lipooligosaccharide (LOS) sialylation but varies widely among LOS from different strains
Activation of toll-like receptor 2 (TLR2) and TLR4/MD2 by Neisseria is independent of capsule and lipooligosaccharide (LOS) sialylation but varies widely among LOS from different strains

Lipooligosaccharide (LOS) structure and capsular polysaccharide of Neisseria meningitidis each greatly influence the virulence of the organism and the quality of host innate immune responses. In this study, we found that production of the proinflammatory cytokine tumor necrosis factor (TNF) by a human monocyte-derived cell line (THP-1) exposed to strains of N. meningitidis lacking capsule and/or with truncated LOS was similar to that elicited by the isogenic wild-type strain. These mutants also exhibited no difference in induction of the interleukin-8 (IL-8) promoter in a transfected HeLa cell system of Toll-like receptor 2 (TLR2) and TLR4/MD2 signaling. However, purified LOS from diverse strains of Neisseria (both N. meningitidis and N. gonorrhoeae) caused widely variant levels of IL-8 promoter induction in cells expressing MD2 that correlated with the production of TNF from THP-1 cells. These data suggest that although modification of the oligosaccharide chain of LOS and/or absence of capsule do not affect cell signaling mediated by TLR4/MD2, fine-structural differences in the LOS do influence signaling through TLR4/MD2 and, through this pathway, influence some of the proinflammatory responses elicited by Neisseria.

Bacterial Capsules, Cell Line, Cytokines, Humans, Lipopolysaccharides, Membrane Glycoproteins, N-Acetylneuraminic Acid, Neisseria gonorrhoeae, Neisseria meningitidis, Receptors, Cell Surface, Species Specificity, Toll-Like Receptor 2, Toll-Like Receptor 4, Toll-Like Receptors, Journal Article, Research Support, Non-U.S. Gov't
0019-9567
3901-8
Pridmore, Alison C
b704c202-afcc-4fde-9169-48e51f9fa0b0
Jarvis, Gary A
ac350cd8-4abb-4bc9-bdc6-2b806440f1ef
John, Constance M
ffc88c2b-852f-4f59-aea6-ccd9d77727b7
Jack, Dominic L
246dc47b-5b5e-4933-9227-d13aafd9cb88
Dower, Steven K
c59b6ed1-57d4-49cb-815c-038a96601ecc
Read, Robert C
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Pridmore, Alison C
b704c202-afcc-4fde-9169-48e51f9fa0b0
Jarvis, Gary A
ac350cd8-4abb-4bc9-bdc6-2b806440f1ef
John, Constance M
ffc88c2b-852f-4f59-aea6-ccd9d77727b7
Jack, Dominic L
246dc47b-5b5e-4933-9227-d13aafd9cb88
Dower, Steven K
c59b6ed1-57d4-49cb-815c-038a96601ecc
Read, Robert C
b5caca7b-0063-438a-b703-7ecbb6fc2b51

Pridmore, Alison C, Jarvis, Gary A, John, Constance M, Jack, Dominic L, Dower, Steven K and Read, Robert C (2003) Activation of toll-like receptor 2 (TLR2) and TLR4/MD2 by Neisseria is independent of capsule and lipooligosaccharide (LOS) sialylation but varies widely among LOS from different strains. Infection and Immunity, 71 (7), 3901-8. (doi:10.1128/IAI.71.7.3901-3908.2003).

Record type: Article

Abstract

Lipooligosaccharide (LOS) structure and capsular polysaccharide of Neisseria meningitidis each greatly influence the virulence of the organism and the quality of host innate immune responses. In this study, we found that production of the proinflammatory cytokine tumor necrosis factor (TNF) by a human monocyte-derived cell line (THP-1) exposed to strains of N. meningitidis lacking capsule and/or with truncated LOS was similar to that elicited by the isogenic wild-type strain. These mutants also exhibited no difference in induction of the interleukin-8 (IL-8) promoter in a transfected HeLa cell system of Toll-like receptor 2 (TLR2) and TLR4/MD2 signaling. However, purified LOS from diverse strains of Neisseria (both N. meningitidis and N. gonorrhoeae) caused widely variant levels of IL-8 promoter induction in cells expressing MD2 that correlated with the production of TNF from THP-1 cells. These data suggest that although modification of the oligosaccharide chain of LOS and/or absence of capsule do not affect cell signaling mediated by TLR4/MD2, fine-structural differences in the LOS do influence signaling through TLR4/MD2 and, through this pathway, influence some of the proinflammatory responses elicited by Neisseria.

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More information

Published date: July 2003
Keywords: Bacterial Capsules, Cell Line, Cytokines, Humans, Lipopolysaccharides, Membrane Glycoproteins, N-Acetylneuraminic Acid, Neisseria gonorrhoeae, Neisseria meningitidis, Receptors, Cell Surface, Species Specificity, Toll-Like Receptor 2, Toll-Like Receptor 4, Toll-Like Receptors, Journal Article, Research Support, Non-U.S. Gov't

Identifiers

Local EPrints ID: 416557
URI: http://eprints.soton.ac.uk/id/eprint/416557
ISSN: 0019-9567
PURE UUID: 50c7a2db-af0f-4ca0-a579-c3739787c499
ORCID for Robert C Read: ORCID iD orcid.org/0000-0002-4297-6728

Catalogue record

Date deposited: 21 Dec 2017 17:30
Last modified: 10 Nov 2021 03:30

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Contributors

Author: Alison C Pridmore
Author: Gary A Jarvis
Author: Constance M John
Author: Dominic L Jack
Author: Steven K Dower
Author: Robert C Read ORCID iD

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