Ingestion of eggs (ova) of the porcine nematode parasite Trichuris suis (TSO) may reduce the severity of autoimmune disorders, however the development of TSO treatment as a useful therapy for autoimmune diseases is hampered by a lack of knowledge on the development of the parasite and the nature of the local immune responses in humans. Here, we used colonoscopy to investigate the development of T. suis and related mucosal and systemic immune responses during TSO treatment in an intestinally healthy male volunteer. TSO treatment induced T. suis-specific serum antibodies, a transient blood eosinophilia, and increases in IFNγ+ and IL4+ cells within the circulating CD4+ T-cell population. Increased expression of genes encoding cytokines (IL4, IL10, IL17 and TGF-β), and transcription factors (FOXP3, GATA3 and RORC) were apparent in the ascending and transverse colon (the predilection site of the worms), whereas only limited changes in gene expression were observed proximally (ileum) and distally (descending colon) to the infected tissue. We further show that T. suis is able to colonise the human colon, with a number of worms developing to a similar size and morphology observed in the natural pig host, and a small number of unembryonated eggs were passed in the faeces, indicating patent infection. Notably, the volunteer experienced a substantial improvement in psoriasis during the course of TSO treatment. Thus, TSO treatment induced a mixed Th1/Th2/T regulatory response at the local site of infection, which was also reflected to some extent in the peripheral circulation. These results, together with the first definitive observations that T. suis can mature to adult size and reproduce in humans, shed new light on the interaction between the human immune system and probiotic helminth treatment, which should facilitate further development of this novel therapeutic option.
Keywords: Helminth therapy; Inflammation; Parasite; Trichuris suis.
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