Helminth antigens modulate TLR-initiated dendritic cell activation.
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.
Kane
Colleen M
CM
Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104, USA.
Cervi
Laura
L
Sun
Jie
J
McKee
Amy S
AS
Masek
Katherine S
KS
Shapira
Sagi
S
Hunter
Christopher A
CA
Pearce
Edward J
EJ
D000818:Animals; D000947:Antigens, Helminth / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D015536:Down-Regulation / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D007155:Immunologic Factors / Q000502:physiology*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis / Q000502:physiology; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000502:physiology*; D012550:Schistosoma mansoni / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D051193:Toll-Like Receptors; D015854:Up-Regulation / Q000276:immunology
D000947:Antigens, Helminth; D007155:Immunologic Factors; D018836:Inflammation Mediators; D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D016753:Interleukin-10; D018664:Interleukin-12