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Neurocysticercal antigens stimulate chemokine secretion from human monocytes via an NF-kappaB-dependent pathway

Neurocysticercal antigens stimulate chemokine secretion from human monocytes via an NF-kappaB-dependent pathway
Neurocysticercal antigens stimulate chemokine secretion from human monocytes via an NF-kappaB-dependent pathway

Neurocysticercosis, infection with larval Taenia solium, is a common, serious neuroparasitic infection. Larval degeneration results in inflammatory cell influx and granuloma formation which leads to clinical symptomatology. The role of chemokines in such cell influx is unknown. We demonstrate that monocyte stimulation by T. solium larval antigen (TsAg) results in a differential profile of CXCL8/IL-8 (146.5+/-8.5ng/ml after 24h), CCL2/MCP-1 (267+/-4 ng/ml after 48 h) and CCL3/MIP-1alpha (1.72+/-0.43 ng/ml after 8 h) secretion. There was coordinate mRNA accumulation reaching maximum at 1h for CCL3 and 2 h for CXCL8 and CCL2. TsAg induced maximal nuclear binding of p65, p50 and c-rel subunits of the transcriptional regulator NF-kappaB by 2 h. IkappaBalpha but not IkappaBbeta was degraded within 10 min before resynthesis by 2 h. Pre-treatment with the broad-spectrum NF-kappaB inhibitor pyrrolidine dithiocarbamate caused complete abrogation of TsAg-induced CCL2 secretion (p=0.005) and 91% reduction of CXCL8 secretion (p=0.0003). TsAg was unable to induce CXCL8 promoter activity in Toll-like receptor (TLR)-2 or TLR-4/MD-2 transfected HeLa cells in the absence of lectins or other adaptor molecules. In summary, our data demonstrate that TsAg induces chemokine secretion via specific pathways dependent on NF-kappaB but not TLR-4/TLR-2, and indicate a potential mechanism whereby larval degeneration results in brain inflammation.

Animals, Antigens, Helminth, Cell Nucleus, Cells, Cultured, Chemokine CCL2, Chemokines, Chemokines, CXC, Cysticercus, Gene Expression, Humans, I-kappa B Proteins, Interleukin-8, Monocytes, NF-KappaB Inhibitor alpha, NF-kappa B, NF-kappa B p50 Subunit, Pyrrolidines, RNA, Messenger, Swine, Thiocarbamates, Toll-Like Receptors, Transcription Factor RelA, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
1286-4579
1732-1740
Uddin, Jasim
24fc0c5e-a30e-47f1-820c-936f7d50a870
Gonzalez, Armando E.
6788e53b-9a88-4d72-9ca7-5c792dcb8e95
Gilman, Robert H.
d948b282-8e0c-43de-aeda-4b8c8a789870
Garcia, Hector H.
39bfb448-5e87-40c7-b688-eda3062fa254
Verastegui, Manuela
cdd2dacd-d713-4e52-9418-1719edb8e3ce
Moore, Lisa J.
13095db5-12ee-47f4-ae09-b1deca4881d3
Evans, Carlton A.W.
8ac2fab5-614b-4da4-8ba8-81b6ef835d49
Read, Robert C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Friedland, Jon S.
9968669f-afe0-4163-9b35-3b476246fd4a
Uddin, Jasim
24fc0c5e-a30e-47f1-820c-936f7d50a870
Gonzalez, Armando E.
6788e53b-9a88-4d72-9ca7-5c792dcb8e95
Gilman, Robert H.
d948b282-8e0c-43de-aeda-4b8c8a789870
Garcia, Hector H.
39bfb448-5e87-40c7-b688-eda3062fa254
Verastegui, Manuela
cdd2dacd-d713-4e52-9418-1719edb8e3ce
Moore, Lisa J.
13095db5-12ee-47f4-ae09-b1deca4881d3
Evans, Carlton A.W.
8ac2fab5-614b-4da4-8ba8-81b6ef835d49
Read, Robert C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Friedland, Jon S.
9968669f-afe0-4163-9b35-3b476246fd4a

Uddin, Jasim, Gonzalez, Armando E., Gilman, Robert H., Garcia, Hector H., Verastegui, Manuela, Moore, Lisa J., Evans, Carlton A.W., Read, Robert C. and Friedland, Jon S. (2006) Neurocysticercal antigens stimulate chemokine secretion from human monocytes via an NF-kappaB-dependent pathway. Microbes and infection, 8 (7), 1732-1740. (doi:10.1016/j.micinf.2006.02.009).

Record type: Article

Abstract

Neurocysticercosis, infection with larval Taenia solium, is a common, serious neuroparasitic infection. Larval degeneration results in inflammatory cell influx and granuloma formation which leads to clinical symptomatology. The role of chemokines in such cell influx is unknown. We demonstrate that monocyte stimulation by T. solium larval antigen (TsAg) results in a differential profile of CXCL8/IL-8 (146.5+/-8.5ng/ml after 24h), CCL2/MCP-1 (267+/-4 ng/ml after 48 h) and CCL3/MIP-1alpha (1.72+/-0.43 ng/ml after 8 h) secretion. There was coordinate mRNA accumulation reaching maximum at 1h for CCL3 and 2 h for CXCL8 and CCL2. TsAg induced maximal nuclear binding of p65, p50 and c-rel subunits of the transcriptional regulator NF-kappaB by 2 h. IkappaBalpha but not IkappaBbeta was degraded within 10 min before resynthesis by 2 h. Pre-treatment with the broad-spectrum NF-kappaB inhibitor pyrrolidine dithiocarbamate caused complete abrogation of TsAg-induced CCL2 secretion (p=0.005) and 91% reduction of CXCL8 secretion (p=0.0003). TsAg was unable to induce CXCL8 promoter activity in Toll-like receptor (TLR)-2 or TLR-4/MD-2 transfected HeLa cells in the absence of lectins or other adaptor molecules. In summary, our data demonstrate that TsAg induces chemokine secretion via specific pathways dependent on NF-kappaB but not TLR-4/TLR-2, and indicate a potential mechanism whereby larval degeneration results in brain inflammation.

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More information

Accepted/In Press date: 2 February 2006
e-pub ahead of print date: 21 April 2006
Published date: June 2006
Keywords: Animals, Antigens, Helminth, Cell Nucleus, Cells, Cultured, Chemokine CCL2, Chemokines, Chemokines, CXC, Cysticercus, Gene Expression, Humans, I-kappa B Proteins, Interleukin-8, Monocytes, NF-KappaB Inhibitor alpha, NF-kappa B, NF-kappa B p50 Subunit, Pyrrolidines, RNA, Messenger, Swine, Thiocarbamates, Toll-Like Receptors, Transcription Factor RelA, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't

Identifiers

Local EPrints ID: 416312
URI: http://eprints.soton.ac.uk/id/eprint/416312
ISSN: 1286-4579
PURE UUID: abeed7f0-49fa-4332-9a9a-db3567e91911
ORCID for Robert C. Read: ORCID iD orcid.org/0000-0002-4297-6728

Catalogue record

Date deposited: 12 Dec 2017 17:30
Last modified: 10 Nov 2021 03:30

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Contributors

Author: Jasim Uddin
Author: Armando E. Gonzalez
Author: Robert H. Gilman
Author: Hector H. Garcia
Author: Manuela Verastegui
Author: Lisa J. Moore
Author: Carlton A.W. Evans
Author: Robert C. Read ORCID iD
Author: Jon S. Friedland

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