Mechanisms regulating monocyte CXCL8 secretion in neurocysticercosis and the effect of antiparasitic therapy

Jasim Uddin, Armando E. Gonzalez, Robert H. Gilman, Lynette H. Thomas, Silvia Rodriguez, Carlton A.W. Evans, Daniel G. Remick, Hector H. Garcia, Jon S. Friedland

Research output: Contribution to journalArticle

Abstract

Neurocysticercosis (NCC) due to infection with Taenia solium is a major cause of epilepsy worldwide. Larval degeneration, which may follow antiparasitic treatment, results in clinical symptoms due to inflammatory cell influx. Mechanisms regulating this are not well understood, but chemokines have a key role. Stimulation of human monocytes by cyst Ags from NCC-infected pigs showed that scolex and membrane Ags drive CXCL8 and CCL2 secretion. Antiparasitic treatment of pigs increased CXCL8 in response to brain, but not muscle, cyst Ags. Cyst-fluid Ags did not elicit monocyte chemokine secretion, inhibited LPS-induced CXCL8 by up to 89%, but did not alter CCL2 secretion. This effect was inhibited by anti-IL-10 Abs. Plasma CXCL8, TNF-α, IL-10, eotaxin, IL-1, IL-1ra, soluble IL-1R-II, and soluble TNFR-I and-II levels were evaluated in 167 NCC patients. Patients had lower plasma CXCL8 and TNF-α concentrations than control subjects. In summary, larval Ags from brain and muscle cysts differentially regulate chemokine secretion. Cyst-fluid inhibits CXCL8, and this is blocked by anti-IL-10 Abs. CXCL8 concentrations are decreased in patient plasma. Following anti-parasitic therapy, scolex and membrane Ags are exposed, and cyst fluid is decreased, leading to inflammatory cell influx. Taken together, the cellular, porcine, and human data may explain, in part, why NCC is usually asymptomatic but may cause proinflammatory symptoms, particularly following treatment.

Original languageEnglish (US)
Pages (from-to)4478-4484
Number of pages7
JournalJournal of Immunology
Volume185
Issue number7
DOIs
StatePublished - Oct 1 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Uddin, J., Gonzalez, A. E., Gilman, R. H., Thomas, L. H., Rodriguez, S., Evans, C. A. W., Remick, D. G., Garcia, H. H., & Friedland, J. S. (2010). Mechanisms regulating monocyte CXCL8 secretion in neurocysticercosis and the effect of antiparasitic therapy. Journal of Immunology, 185(7), 4478-4484. https://doi.org/10.4049/jimmunol.0904158