Helminth antigens modulate TLR-initiated dendritic cell activation.
J Immunol, 2004/12/15;173(12):7454-61.
Kane CM[1], Cervi L, Sun J, McKee AS, Masek KS, Shapira S, Hunter CA, Pearce EJ
Affiliations
PMID: 15585871
Impact factor: 5.426
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-kappaB 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.
MeSH terms
Animals; Antigens, Helminth; Cell Differentiation; Cells, Cultured; Dendritic Cells; Down-Regulation; Gene Expression Regulation; Immunologic Factors; Inflammation Mediators; Interleukin-10; Interleukin-12; Ligands; Lipopolysaccharides; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Cell Surface; Schistosoma mansoni; Signal Transduction; Toll-Like Receptors; Up-Regulation
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