The role and interaction of Treg cells during schistosomiasis
Final Report Abstract
Over the last decade, research into the immunological relationship between parasites and hosts has identified several mechanisms which aid the survival of both species. In essence, the parasite has developed techniques in which it encourages its recognition by the host and in doing so, elicits help from the host’s immune system for its own benefit. In Schistosoma mansoni, this is very clear when one observes the almost silent response of DC to schistosomal antigens. In addition, components within SEA dampen TLR-triggered responses. One of the highlights of our research over the last two years has been the elucidation that other components within SEA trigger the activation of the Nlrp3 inflammasome. Indeed we found that these protein-based antigen signals through Dectin-2 a receptor for C-type lectins. These results have formed the basis for a new project. Upon publication, this work was considered in the top 2% of research by L. Lenz, University of Washington and T. Nutmann, NIH, USA in Faculty of 1000 Biology. In addition, it has been noted in a current review by G. Brown, Aberdeen University, UK. Alongside the immunomodulating capacity of SEA on innate cells, it also plays a strong role in the development of granulomas, the main morbidity factor of schistosomiaisis. This granulomatous inflammation arises from adaptive immune reactions of the host to trapped eggs which fail to pass (perhaps even on purpose) into the gut lumen. Our published work has identified some aspect of Treg activity during S. mansoni infection. We described that lack of Treg cells elicits violent immunopathology in the host with elevated Th1 responses. Simultaneously, viable eggs were destroyed by the immune system indicating that schistosome-induced Treg cells not only regulated immune responses to self but are “helminth-friendly” too. Moreover, infected TLR2-/- mice displayed the same phenotype as those without Treg cells and we determined that this was due to the failure of Treg cells to expand during infection. Over the two year funding period our group has been able to verify many of the aims stated in our original proposal. We found a selection of genes that were exclusively upregulated in Treg from infected mice but surprisingly there was no differences between Treg from WT infected and TLR2-/- infected mice even though the latter suffered from strong immunopathology. Using knockout mice we would like to continue our research on Treg by studying the functional role of these genes during infection especially with regards to developing pathology and suppressive capacities. These studies also formed the basis of our application to the SBF Tr22 of which we have become participants.
Publications
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Immunopathology in schistosomiasis is controlled by antigen-specific regulatory T cells primed in the presence of TLR2. Eur J Immunol. 37:2174-2184
Layland, L.E., Rad, R., Wagner, H. and da Costa, C.U.
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2010. Pronounced phenotype in activated regulatory T cells during a chronic helminth infection. J Immunol.184:713-724
Layland, L.E., Mages, J., Loddenkemper, C., Hoerauf, A., Wagner, H., Lang, R. and da Costa, C.U.
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2010. Schistosoma mansoni triggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses. Proc Natl Acad Sci U S A. 107:20459-64
Ritter, M., Gross, O., Kays, S., Ruland, J., Nimmerjahn, F., Saijo, S., Tschopp, J., Layland, L.E. and Prazeres da Costa, C.
