Helminth antigens modulate TLR-initiated dendritic cell activation

Colleen M. Kane, Laura Cervi, Jie Sun, Amy S. McKee, Katherine S. Masek, Sagi Shapira, Christopher A. Hunter, Edward J. Pearce

Research output: Contribution to journalArticle

191 Scopus citations

Abstract

There is increasing awareness that helminth infections can ameliorate proinflammatory conditions. In part, this is due to their inherent ability to induce Th2 and, perhaps, regulatory T cell responses. However, recent evidence indicates that helminths also have direct anti-inflammatory effects on innate immune responses. In this study, we address this issue and show that soluble molecules from the eggs of the helminth parasite Schistosoma mansoni (SEA) suppress LPS-induced activation of immature murine dendritic cells, including MHC class II, costimulatory molecule expression, and IL-12 production. SEA-augmented LPS-induced production of IL-10 is in part responsible for the observed reduction in LPS-induced IL-12 production. However, analyses of IL-10-/- DC revealed distinct IL-10-independent suppressive effects of SEA. IL-10-independent mechanisms are evident in the suppression of TLR ligand-induced MAPK and NF-κB signaling pathways. Microarray analyses demonstrate that SEA alone uniquely alters the expression of a small subset of genes that are not up-regulated during conventional TLR-induced DC maturation. In contrast, the effects of SEA on TLR ligand-induced DC activation were striking: when mixed with LPS, SEA significantly affects the expression of >100 LPS-regulated genes. These findings indicate that SEA exerts potent anti-inflammatory effects by directly regulating the ability of DC to respond to TLR ligands.

Original languageEnglish (US)
Pages (from-to)7454-7461
Number of pages8
JournalJournal of Immunology
Volume173
Issue number12
DOIs
StatePublished - Dec 15 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Kane, C. M., Cervi, L., Sun, J., McKee, A. S., Masek, K. S., Shapira, S., Hunter, C. A., & Pearce, E. J. (2004). Helminth antigens modulate TLR-initiated dendritic cell activation. Journal of Immunology, 173(12), 7454-7461. https://doi.org/10.4049/jimmunol.173.12.7454