Authors

V Shek¹; HH Smits²; HJ McSorley¹;  ¹ University of Dundee, UK;  ² Leiden University Medical Centre, Netherlands

Discussion

Type 2 immune responses are commonly associated with host defence against helminth infections and the development of allergic inflammation. Helminths are highly effective at initiating immunoregulatory mechanisms; there is increasing interest in dissecting out the regulatory pathways they induce and identifying the specific molecular mediators from parasites involved in these pathways.

IL-4 inducing Principle from Schistosome Eggs (IPSE) is a glycoprotein secreted from the eggs of Schistosoma mansoni and has been shown to modulate the host immune response by inducing IL-4 production in basophils and IL-10 production in regulatory B cells. In addition to its immunomodulatory capacity, IPSE is an interesting molecule due to its unusual mode of action: IPSE contains a secretory signal peptide at the N-terminus, enabling trafficking of the protein to the secretory pathway, and a nuclear localisation sequence (NLS) that directs the protein to the nucleus. Typically, proteins possess only one of these signals, as they are either secreted or localised to the nucleus. In addition to IPSE, S. japonicum-derived molecule Sj16 serves as another example of a NLS-containing immunomodulatory molecule. Sj16 has been shown to induce IL-10 production and inhibit the maturation of dendritic cells upon entering the host nucleus. Thus, we hypothesised that the presence of a NLS on helminth molecules could be a mechanism used by parasites to modulate the host immune response by altering host cellular activity.

Here, we treated human monocyte derived dendritic cells (MoDC) with S. mansoni soluble egg antigen (SEA) for 24 hrs and carried out subcellular fractionation and DIA proteomics to identify other Schistosome-derived proteins like IPSE that migrate into host cell nuclei.

The mass spectrometry results identified 7700 human and 550 S. mansoni proteins, and IPSE was significantly enriched in the nuclear fraction of SEA-treated MoDCs alongside 14 other S. mansoni proteins. The proteomics data set will provide new insights into how the host immune response is altered during S. mansoni infection, which may prove beneficial for developing novel anthelmintics.