Abstract
BackgroundDuring the pre-patent stage of infection, juvenile Schistosoma blood flukes co-opt signals from the adaptive immune system to facilitate parasite development, but the types of responses that are induced at this early stage of infection, and the parasite antigens they target, have not been characterized.ResultsThrough analysis of experimental pre-patent infections, we show that the S. mansoni cysteine protease SmCB1 is rapidly targeted by an antigen-specific IgE response. The induction of this response is independent of schistosome eggs as infection with male or female worms alone also induced SmCB1-specific IgE. We also show that the SmCB1-specific IgE response is dependent on cognate CD4+ T cell help and IL-4, suggesting that pre-patent Th2 responses provide T cell help for the SmCB1-specific IgE response. Finally, exposed human subjects also produced IgE against SmCB1.ConclusionsOur data demonstrate that, like eggs, schistosome worms also induce functional type 2 responses and that a parasite cysteine protease is an inducer of type 2 responses during the early stages of schistosome infection.
Highlights
During the pre-patent stage of infection, juvenile Schistosoma blood flukes co-opt signals from the adaptive immune system to facilitate parasite development, but the types of responses that are induced at this early stage of infection, and the parasite antigens they target, have not been characterized
Rapid induction of SmCB1-specific IgE in the absence of schistosome eggs While previous reports suggested that CD4+ T cells primarily mount Th1 responses to worm antigens during pre-patent infection [7,13], we recently showed that schistosome worms induce IL-4-producing CD4+ T cells during pre-patent infection, which could serve as a source of Th2 help for the IgE
T cell help and IL-4 are required for SmCB1-specific IgE production during pre-patent infection To test whether worm-induced pre-patent Th2 responses, such as the those we have described recently [14], are involved in class-switching of the anti-SmCB1 response to IgE, we tested whether the SmCB1-specific IgE response was dependent on CD4+ T cell help and IL-4
Summary
During the pre-patent stage of infection, juvenile Schistosoma blood flukes co-opt signals from the adaptive immune system to facilitate parasite development, but the types of responses that are induced at this early stage of infection, and the parasite antigens they target, have not been characterized. Despite their large size and complex multicellular structure, schistosomes display a remarkable ability to survive for years within the mammalian bloodstream, remaining viable and reproductively active in the face of potentially damaging immune responses. Specific worm antigens have been identified in the context of immune resistance, such as in vaccinated animals [15,16,17] and putatively resistant human subjects [18,19,20], but the significance of these antigens during normal permissive infection has not been explored
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