Omega-1, a glycoprotein secreted by Schistosoma mansoni eggs, drives Th2 responses

Abstract

Soluble egg antigens of the parasitic helminth Schistosoma mansoni (S. mansoni egg antigen [SEA]) induce strong Th2 responses both in vitro and in vivo. However, the specific molecules that prime the development of Th2 responses have not been identified. We report that omega-1, a glycoprotein which is secreted from S. mansoni eggs and present in SEA, is capable of conditioning human monocyte-derived dendritic cells in vitro to drive T helper 2 (Th2) polarization with similar characteristics as whole SEA. Furthermore, using IL-4 dual reporter mice, we show that both natural and recombinant omega-1 alone are sufficient to generate Th2 responses in vivo, even in the absence of IL-4R signaling. Finally, omega-1–depleted SEA displays an impaired capacity for Th2 priming in vitro, but not in vivo, suggesting the existence of additional factors within SEA that can compensate for the omega-1–mediated effects. Collectively, we identify omega-1, a single component of SEA, as a potent inducer of Th2 responses.

Schistosomamansonitriggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses

“…SEA is a complex mixture of proteins, glycoproteins, and glycolipids (28,29), and our studies show that SEA-mediated IL-1β production was abolished upon heat inactivation and proteinase K digestion, demonstrating that the responsible component might be a protein. Interestingly, the inactivation of SEA did not alter the TNF-α suppression, suggesting that different components within SEA can act in tandem and thus balance ongoing immune responses.…”

“…This finding presents the possibility that the potential Syk-coupled receptor, which is activated by SEA, is a lectin receptor. In association, C-type lectin receptors have been shown to partially mediate the internalization of these antigens, which may highlight the necessity of sugar components in SEA (6, 28,29). This study has deciphered that SEA specifically signals through the C-type lectin receptor Dectin-2, but not Dectin-1 or other receptors such as CD206, CD36, and DAP12.…”

“…Therefore, we consider that this mechanism is not used by SEA. Several studies have postulated that the inflammasome is triggered by different upstream events such as potassium (K + ) efflux or ROS production (17,19,(28)(29)(30). To elucidate the role of these intermediary signals, we treated BMDCs with potassium chloride (Fig.…”

Helminths and dendritic cells: Sensing and regulating via pattern recognition receptors, Th2 and Treg responses

“…A feature shared by many helminths is their capacity to suppress TLR-mediated DC activation by microbial PAMP. Numerous studies have reported the inhibitory effects of helminth-derived components on TLR-induced activation as determined by pro-inflammatory cytokine production and expression of MHC class II/costimulatory molecules [28,[33][34][35][36][37][38][39]. The pathways underlying this suppression are, however, still poorly understood.…”

Dendritic cells treated with crude Plasmodium berghei extracts acquire immune‐modulatory properties and suppress the development of autoimmune neuroinflammation

“…43,44 In addition, soluble egg antigens from S. mansoni is enriched in omega-1, which modulates DCs and induces the expression of Foxp3 in T cells in vitro. 45,46 Although the restrained immune response in malaria and schistosomiasis is a problem, the impairment in DC function may become useful for the control of chronic inflammatory conditions. Likewise, DCs exposed to soluble egg antigens and omega-1 acquire modulatory properties and induces Treg cells in CD4 + T cells from non-obese diabetic (NOD) mice, reducing the incidence of spontaneous diabetes.…”