Parasitic worms have a remarkable ability to modulate host immune responses through several mechanisms including excreted/secreted proteins (ESP), yet the exact nature of these proteins and their targets often remains elusive. Here, we performed mass spectrometry analyses of ESP (TsESP) from larval and adult stages of the pig whipworm Trichuris suis (Ts) and identified ~350 proteins. Transcriptomic analyses revealed large subsets of differentially expressed genes in the various life cycle stages of the parasite. Exposure of bone marrow-derived macrophages and dendritic cells to TsESP markedly diminished secretion of the pro-inflammatory cytokines TNFα and IL-12p70. Conversely, TsESP exposure strongly induced release of the anti-inflammatory cytokine IL-10, and also induced high levels of nitric oxide (NO) and upregulated arginase activity in macrophages. Interestingly, TsESP failed to directly induce CD4+ CD25+ FoxP3+ regulatory T cells (Treg cells), while OVA-pulsed TsESP-treated dendritic cells suppressed antigen-specific OT-II CD4+ T cell proliferation. Fractionation of TsESP identified a subset of proteins that promoted anti-inflammatory functions, an activity that was recapitulated using recombinant T. suis triosephosphate isomerase (TPI) and nucleoside diphosphate kinase (NDK). Our study helps illuminate the intricate balance that is characteristic of parasite-host interactions at the immunological interface, and further establishes the principle that specific parasite-derived proteins can modulate immune cell functions.

BenedictDevereaux is a consultant and member on advisory board for Boston Scientific. Milan Bassan is a consultant for Boston Scientific. Payal Saxena is a consultant for Boston Scientific. Thawee Ratanachu-EK is a proctor for Boston Scientific. All other authors have no relevant conflicts of interest to disclose. Financial support: There were no sources of financial grants or other funding for this study.

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The aim of this study was to evaluate the safety and efficacy of Bacillus Calmette-Guerin, polysaccharide nucleic acid (BCG-PSN) therapy in the treatment of oral and cutaneous LP. Twenty-four LP patients were included in this study and classified randomly into; Oral LP group (OLP), 11 patients and Cutaneous LP group (CLP), 13 patients. All patients received intradermal injections of BCG-PSN, twice weekly for three weeks. Patients with complete response were followed up for 3 months. The assessment in OLP was based on the reduction in the treated area, (Reticulation/Erythema/Ulceration) REU scoring system and numerical rating scale (NRS). CLP evaluated by the response to treatment as (complete, partial and no response) and visual analogue scale (VAS). There were highly significant differences in the diminution of lesion areas (p < .006), NRS scores (p < .001), REU score (p < .011), and VAS (p < .001) after treatment. The majority of patients achieved complete response after 3-week management. The BCG-PNS is safe and effective in the treatment of oral and cutaneous LP.

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