The major component in schistosome eggs responsible for conditioning dendritic cells for Th2 polarization is a T2 ribonuclease (omega-1).
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.
Steinfelder
Svenja
S
Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Andersen
John F
JF
Cannons
Jennifer L
JL
Feng
Carl G
CG
Joshi
Manju
M
Dwyer
Dennis
D
Caspar
Pat
P
Schwartzberg
Pamela L
PL
Sher
Alan
A
Jankovic
Dragana
D
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D002448:Cell Adhesion; D002454:Cell Differentiation; D017077:Culture Media, Conditioned; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D015801:Helminth Proteins / Q000276:immunology*; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010063:Ovum / Q000276:immunology; D012260:Ribonucleases / Q000037:antagonists & inhibitors / Q000276:immunology*; D012550:Schistosoma mansoni / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*
D000947:Antigens, Helminth; D017077:Culture Media, Conditioned; D015801:Helminth Proteins; D012260:Ribonucleases