Trichinella spiralis, as well as its muscle larvae excretory–secretory products (ES L1), given either alone or via dendritic cells (DCs), induce a tolerogenic immune microenvironment in inbred rodents and successfully ameliorate experimental autoimmune encephalomyelitis. ES L1 directs the immunological balance away from T helper (Th)1, toward Th2 and regulatory responses by modulating DCs phenotype. The ultimate goal of our work is to find out if it is possible to translate knowledge obtained in animal model to humans and to generate human tolerogenic DCs suitable for therapy of autoimmune diseases through stimulation with ES L1. Here, the impact of ES L1 on the activation of human monocyte-derived DCs is explored for the first time. Under the influence of ES L1, DCs acquired tolerogenic (semi-matured) phenotype, characterized by low expression of HLA-DR, CD83, and CD86 as well as moderate expression of CD40, along with the unchanged production of interleukin (IL)-12 and elevated production of IL-10 and transforming growth factor (TGF)-β, compared to controls. The interaction with DCs involved toll-like receptors (TLR) 2 and 4, and this interaction was mainly responsible for the phenotypic and functional properties of ES L1-treated DCs. Importantly, ES L1 potentiated Th2 polarizing capacity of DCs, and impaired their allo-stimulatory and Th1/Th17 polarizing properties. Moreover, ES L1-treated DCs promoted the expansion of IL-10- and TGF-β- producing CD4+CD25hiFoxp3hi T cells in indolamine 2, 3 dioxygenase (IDO)-1-dependent manner and increased the suppressive potential of the primed T cell population. ES L1-treated DCs retained the tolerogenic properties, even after the challenge with different pro-inflammatory stimuli, including those acting via TLR3 and, especially TLR4. These results suggest that the induction of tolerogenic properties of DCs through stimulation with ES L1 could represent an innovative approach for the preparation of tolerogenic DC for treatment of inflammatory and autoimmune disorders.

Modulation of the immune response by helminths involves the excretory ⁄ secretory (ES) products released by these parasites. These products include proteases, protease inhibitors, venom allergen homologues, glycolytic enzymes, lectins, lipids and glycans, which together or individually could be potential immunomodulators (14,15). There are only few studies on T. spiralis products and their effect on the immune response (16,17). We have previously shown that ES products from T. spiralis (TspES) suppress DC maturation induced by the S-form of Escherichia coli LPS but not by the R-form of Neisseria meningitidis LPS (16). Because the S-form of LPS requires CD14 for TLR4 activation whereas the R-form does not (18-20), a possible role for CD14 in this suppression was suggested.Here, we aim at studying further the effect of TspES on DC maturation and on T cell activation. We found that the suppressive effect of TspES on DC maturation does not depend on the form of the LPS used, and therefore, it is independent of CD14. In addition, we show that the suppressive effect of TspES on DC maturation is restricted to TLR4 and that these helminth products interfere with the expression of several genes related to the TLR-mediated signal transduction pathways. Using splenocytes derived from OVA-TCR transgenic D011.10 mice, we show that TspES induce in vitro the expansion of CD4 + CD25 + Foxp3 + Treg cells in a TGF-b-dependent manner. These findings contribute to our understanding on the mechanisms involved in the immunoregulation induced by T. spiralis.

These results demonstrate that the protective effect of T. spiralis on EAAI increases as infection progresses from the acute to the chronic phase. Here, Treg cells may play an essential role in the suppression of EAAI. Elucidating the mechanisms and molecular helminth structures responsible for this regulatory process is relevant to develop alternative tools for preventing or treating allergic asthma.

Toxocara canis and Toxocara cati are roundworms of dogs and cats that can also infect humans worldwide. Although these parasites do not reach the adult stage in the human host the larvae migrate to different organs and can persist for many years. Migration of larvae through the lungs may result in respiratory distress such as wheezing, coughs, mucous production and hyper-reactivity of the airways. Epidemiological and experimental studies suggest that infection with this helminth contributes to the development of allergic manifestations, including asthma. These findings are however conflicting since in others studies no association between these two immunopathologies has been found. This article reviews information on Toxocara spp. and findings from epidemiological and experimental studies on the association between Toxocara infection and allergic manifestations. In addition, the immunological mechanisms and the factors involved in the helminth allergy-association are discussed.