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

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

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12 Scopus citations

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 ± 8.5 ng/ml after 24 h), CCL2/MCP-1 (267 ± 4 ng/ml after 48 h) and CCL3/MIP-1α (1.72 ± 0.43 ng/ml after 8 h) secretion. There was coordinate mRNA accumulation reaching maximum at 1 h 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-κB by 2 h. IκBα but not IκBβ was degraded within 10 min before resynthesis by 2 h. Pre-treatment with the broad-spectrum NF-κB 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-κB but not TLR-4/TLR-2, and indicate a potential mechanism whereby larval degeneration results in brain inflammation. © 2006 Elsevier SAS. All rights reserved.
Original languageAmerican English
Pages (from-to)1732-1740
Number of pages9
JournalMicrobes and Infection
DOIs
StatePublished - 1 Jun 2006
Externally publishedYes

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    Uddin, J., Gonzalez, A. E., Gilman, R. H., Garcia, H. H., Verastegui, M., Moore, L. J., Evans, C. A. W., Read, R. C., & Friedland, J. S. (2006). Neurocysticercal antigens stimulate chemokine secretion from human monocytes via an NF-κB-dependent pathway. Microbes and Infection, 1732-1740. https://doi.org/10.1016/j.micinf.2006.02.009