Abstract
Schistosomes are causative agents of human schistosomiasis, which is endemic in tropical and subtropical areas of the world. Adult schistosomes can survive in their final hosts for several decades, and they have evolved various strategies to overcome the host immune response. Consequently, understanding the mechanisms that regulate parasitic cell survival will open avenues for developing novel strategies against schistosomiasis. Our previous study suggested that an inhibitor of apoptosis protein in Schistosoma japonicum (SjIAP) may play important roles in parasitic survival and development. Here, we demonstrated that SjIAP can negatively regulate cellular apoptosis in S. japonicum by suppressing caspase activity. Immunohistochemistry analysis indicated that SjIAP ubiquitously expressed within the worm body including the tegument. Silencing of SjIAP expression via small interfering RNA led to destruction of the tegument integrity in schistosomes. We further used co-immunoprecipitation to identify interaction partners of SjIAP and revealed the tegument protein SjTeg-20 as a putative interacting partner of SjIAP. The interaction between SjIAP and SjTeg-20 was confirmed by a yeast two-hybrid (Y2H) assay. Moreover, results of a TUNEL assay, RNA interference, scanning and transmission electron microscopy, caspase assays, transcript profiling, and protein localization of both interacting molecules provided first evidence for an essential role of SjIAP and SjTeg-20 to maintain the structural integrity of the tegument by negatively regulating apoptosis. Taken together, our findings suggest that the cooperative activities of SjIAP and SjTeg-20 belong to the strategic inventory of S. japonicum ensuring survival in the hostile environment within the vasculature of the final host.
Highlights
As one of the neglected tropical diseases, schistosomiasis is an important public health concern affecting more than 200 million people in 78 tropical and subtropical countries [1]
We demonstrated that an inhibitor of apoptosis protein of Schistosoma japonicum (SjIAP) governs the integrity of the tegument of schistosomes by inhibiting cellular apoptosis of the parasite
Further studies revealed that SjTeg-20, an S. japonicum tegumental protein, cooperates with SjIAP to inhibit apoptosis in schistosomes
Summary
As one of the neglected tropical diseases, schistosomiasis is an important public health concern affecting more than 200 million people in 78 tropical and subtropical countries [1]. Paired adult schistosomes can survive in the final host for several decades. This longevity along with the production of a large number of eggs causes the pathologic consequences and contributes to disease spreading. Uncovering the parasite’s principles of survival in an otherwise aggressive host environment will provide valuable insights into parasite-host interaction which may help to find novel intervention strategies against schistosomiasis. These are urgently needed in face of the facts that there is no vaccine available and only one drug, praziquantel, which is widely used to fight the disease [2]
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