Abstract
Helminth-induced Th2 polarization is associated with down-regulated dendritic cell (DC) function but the underlying molecular mechanism remains elusive due to the poor characterization of helminth molecules with Th2-inducing activity. During Schistosoma mansoni infection egg, but not worm, Ag are a target of a strong Th2 response. Moreover, when injected in naïve mice schistosome eggs or water-soluble egg extract (SEA) have an intrinsic ability to promote development of Th2 cells. Using as a read-out an in vitro model of CD4+ T cell priming with CD11c+ splenic DC we demonstrated that SEA fractions containing molecule(s) with an approximate MW of 30 kD selectively promote Th2 polarization and down-regulate DC functions. Moreover, similar positive fractions were isolated from preparations containing egg excretory/secretory molecules. The N-terminal sequence of the latter identified the S. mansoni enzyme Ribonuclease T2 as the active component and this was further confirmed with the recombinant protein. S. mansoni ribonuclease is the first chemically defined protein with Th2-promoting activity known to act on dendritic cells.
