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¹ Immunobiology Section and ² Cell Biology Section, Laboratory of Parasitic Diseases and ³ Vector Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases and ⁴ National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892

CORRESPONDENCE Dragana Jankovic: DJankovic{at}niaid.nih.gov OR Alan Sher: ASher{at}niaid.nih.gov

Schistosoma mansoni eggs contain factors that trigger potent Th2 responses in vivo and condition mouse dendritic cells (DCs) to promote Th2 lymphocyte differentiation. Using an in vitro bystander polarization assay as the readout, we purified and identified the major Th2-inducing component from soluble egg extract (SEA) as the secreted T2 ribonuclease, omega-1. The Th2-promoting activity of omega-1 was found to be sensitive to ribonuclease inhibition and did not require MyD88/TRIF signaling in DCs. In common with unfractioned SEA, the purified native protein suppresses lipopolysaccharide-induced DC activation, but unlike SEA, it fails to trigger interleukin 4 production from basophils. Importantly, omega-1–exposed DCs displayed pronounced cytoskeletal changes and exhibited decreased antigen-dependent conjugate formation with CD4⁺ T cells. Based on this evidence, we hypothesize that S. mansoni omega-1 acts by limiting the interaction of DCs with CD4⁺ T lymphocytes, thereby lowering the strength of the activation signal delivered.

S. Steinfelder's present address is German Rheumatism Research Center and Charité Research Center for ImmunoSciences, 10117 Berlin, Germany.

Abbreviations used: BMDC, bone marrow–derived DC; DEPC, diethyl pyrocarbonate; ICS, intracellular cytokine staining; PI, propidium iodine; SEA, soluble egg extract; SN, supernatant; Tg, transgenic; TLR, Toll-like receptor.

© 2009 The Rockefeller University Press
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