Abstract
Resistance to Schistosoma mansoni infection has been correlated with IgE responses to the adult worm. Molecular targets of this response are gaining interest as markers of immunity and as indicators of allergenic properties. Few protein families contain IgE antigens (allergens) and one of the most highly represented are the tropomyosins. Alternative splicing generates numerous tropomyosin isoforms, which in parasites is likely to induce a range of anti-tropomyosin responses in the host. Here we examine human IgE and the counteracting IgG4 responses to splice variants of S. mansoni tropomyosin (SmTpm). It was possible to show life-cycle transcription profiles for 12 of 20 predicted splice variants from the four SmTpm genes. We expressed recombinant protein of four variants of TpmII (TpmII.4, 8, 3 and 7) with considerable differences in sequence. TpmII.4 and 8 were muscle, and TpmII.3 and 7 non-muscle, types. IgE and IgG4 responses to all four proteins were measured in a population of 228 infected boys and men (7–76years) from a region of Uganda endemic for S. mansoni. Levels of these antibodies were not dependent on age and did not change following anthelminthic treatment. IgE to TpmII.3 was common in the cohort (>60%) and IgG4 to TpmII.3 less so (33%). IgE to TpmII.7 was rare (6.5%), but IgG4 to TpmII.7 was more common (49%). In regression analysis, a detectable IgE response to TpmII.3 was associated with reduced re-infection 2years after treatment and an IgG4 response to TpmII.7 with increased re-infection. Different isoforms generated by alternative splicing are targeted by different components of the anti-Tpm IgE/IgG4 response. Only some of these are associated with immunity.
Highlights
Infection with Schistosoma mansoni is a serious health problem in sub-Saharan Africa
We designed a nested PCR strategy to determine which of the putative splice variants of the remaining four genes were transcribed using cDNA prepared from seven life cycle stages of S. mansoni as well as isolated heads and tails of cercariae (Table 1)
Alternative splicing of mRNA is an important process in Schistosoma spp., contributing to the range of proteins required for parasite development and interaction with the host (Verjovski-Almeida and DeMarco, 2011)
Summary
Infection with Schistosoma mansoni is a serious health problem in sub-Saharan Africa. We have suggested that are the IgE-mediated processes in allergic and anti-worm responses the same, but so are the types of molecules targeted (Fitzsimmons and Dunne, 2009). Allergens come from a small number of protein families (Radauer et al, 2008) and the anti-worm IgE targets discovered far are all from these families (Fitzsimmons and Dunne, 2009). IgE responses to a number of these proteins (SmTAL1, 3 and 5) have been associated with resistance to infection (Dunne et al, 1997; Fitzsimmons et al, 2012b)
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