Abstract
Several studies indicate that certain helminths suppress the host immune responses. This suppression may benefit the parasite since it increases the chances of survival in their host. By doing so, the hosts may also benefit due to concomitant reduction of immune pathology associated with allergies and autoimmune diseases. The aim
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of the studies described in this thesis was to investigate the mechanisms by which Trichinella spiralis modulate the host immune responses. We also investigated the effect of Trichinella infection on experimental allergic airway inflammation (EAAI). In addition, as a spin-off from this study we examined the potential use of parasite glycans to develop new tools for the serodiagnosis of T. spiralis infection. Our results indicate that T. spiralis excretory/ secretory (TspES) antigens completely inhibited dendritic cell (DC) maturation induced by Escherichia coli LPS. In contrast, DC maturation induced by LPS from another bacterium, Neisseria meningitidis, was not affected by TspES. In conclusion, T. spiralis ES antigens lead to suppression of DC maturation but this effect depends on the on the bacterial source of LPS. To characterize further the effect of TspES on DC maturation, we used other LPS forms derived from different bacteria. We found that TspES suppress DC maturation induced by enterobacterial LPS. During migration through the intestinal wall, Trichinella larvae may drag bacteria on their surface which could cause septic shock. Suppressing the effect of LPS from the dragged bacteria may be a strategy to avoid a septic shock and keep the host alive. We also found 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. In addition, we showed that TspES induce the expansion of regulatory T cells in vitro in a TGF-β-dependent manner. We also investigated whether infection with this helminth modulate the course of allergic asthma. Our data showed that the chronic as well as the acute phase of Trichinella infection protects against EAAI. This protective effect of T. spiralis on EAAI increases as infection progresses from the acute to the chronic phase. We also found that regulatory T cells may play an essential role in the suppression of EAAI. Infection as a therapy is not an option for the treatment of allergy since T. spiralis infection could have adverse consequences for the infected patients. Therefore, isolation of the T. spiralis molecules that modulate the host-immune response is relevant for the development of new therapies for allergic diseases. Among the helminth molecules responsible for the immunomodulation of the host immune responses, certain glycans have been suggested to play an essential role. They have also been reported to be involved in the generation of host antibody responses during infection which make them excellent targets for diagnostic purposes. We show that specific parasite glycans can be identified by using sera of infected patients and glycan microarrays. In addition, we demonstrated that an ELISA using the identified glycans has a high sensitivity for serodiagnosis of trichinellosis
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