Protection against allergic airway inflammation during the chronic and acute phases of Trichinella spiralis infection.

BACKGROUND: Modulation of the host immune response by helminths has been reported to be essential for parasite survival and also to benefit the host by suppressing inflammatory diseases such as allergies. We have previously shown that excretory-secretory products of Trichinella spiralis muscle larvae have immunomodulatory properties and induce in vitro the expansion of CD4(+) CD25(+) FOXP3(+) Treg cells in a TGF-ß-dependent manner. OBJECTIVE: We aimed at determining the effect of the acute (intestinal) and the chronic (muscle) phase of T. spiralis infection on experimental allergic airway inflammation (EAAI) to Ovalbumin (OVA) and the involvement of Treg cells. METHODS: The chronic phase was established before OVA-sensitization/challenge and the acute phase at two-time points, before and after OVA-sensitization. Mice were infected with 400 T. spiralis larvae and after euthanasia different pathological features of EAAI were measured. Adoptive transfer of CD4(+) T cells from Trichinella infected mice to OVA sensitized/challenged recipients was also performed. RESULTS: We found that the chronic as well as the acute phase of Trichinella infection suppress EAAI as indicated by reduction in airway inflammation, OVA-specific IgE levels in sera, Th2-cytokine production and eosinophils in bronchoalveolar lavage. This protective effect was found to be stronger during the chronic phase and to be associated with increased numbers of splenic CD4(+) CD25(+) FOXP3(+) Treg cells with suppressive activity. Adoptive transfer of splenic CD4(+) T cells from chronically infected mice with elevated numbers of Treg cells resulted in partial protection against EAAI. CONCLUSIONS AND CLINICAL RELEVANCE: 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.

Trichinella spiralis-secreted products modulate DC functionality and expand regulatory T cells in vitro.

Helminths and their products can suppress the host immune response which may benefit parasite survival. Trichinella spiralis can establish chronic infections in a wide range of mammalian hosts including humans and mice. Here, we aim at studying the effect of T. spiralis muscle larvae excretory/secretory products (TspES) on the functionality of DC and T cell activation. We found that TspES suppress in vitro DC maturation induced by both S- and R-form lipopolysaccharide(LPS) from enterobacteria. Using different toll-like receptor (TLR) agonists, we show that the suppressive effect of TspES on DC maturation is restricted to TLR4. These helminth products also interfere with the expression of several genes related to the TLR-mediated signal transduction pathways. To investigate the effect of TspES on T cell activation, we used splenocytes derived from OVA-TCR transgenic D011.10 that were incubated with OVA and TspES-pulsed DC. Results indicate that the presence of TspES resulted in the expansion of CD4(+) CD25(+) Foxp3+ T cells. These regulatory T (Treg) cells were shown to have suppressive activity and to produce TGF-ß. Together these results suggest that T. spiralis secretion products can suppress DC maturation and induce the expansion of functional Treg cells in vitro.

Suppression of dendritic cell maturation by Trichinella spiralis excretory/secretory products.

Evidence from experimental studies indicates that during chronic infections with certain helminth species a regulatory network is induced that can down-modulate not only parasite-induced inflammation but also reduce other immunopathologies such as allergies and autoimmune diseases. The mechanisms however, and the molecules involved in this immunomodulation are unknown. Here, we focus on the effect of Trichinella spiralis excretory/secretory antigens (TspES) on the innate immune response by studying the effect of TspES on DC maturation in vitro. Bone marrow-derived DC from BALB/c mice were incubated with TspES either alone or in combination with LPS derived from two different bacteria. As indicators of DC maturation, the cytokine production (IL-1alpha, IL-6, IL-10, IL-12p70 and TNF-alpha) and the expression of various surface molecules (MHC-II, CD40, CD80 and CD86) were measured. Results indicate that while TspES alone did not change the expression of the different surface molecules or the cytokine production, it completely inhibited DC maturation induced by Escherichia coli LPS (E. coli LPS). In contrast, DC maturation induced by LPS from another bacterium, Neisseria meningitidis, was not affected by TspES. These results were confirmed using TLR4/MD2/CD14 transfected HEK 293 cells. In conclusion, T. spiralis ES antigens lead to suppression of DC maturation but this effect depends on the type of LPS used to activate these cells.