Harnessing immunomodulatory mechanisms of Trichinella spiralis to design novel nanomedical approaches for restoring self-tolerance in autoimmunity.

The rapid increase in the prevalence of autoimmune diseases in recent decades, especially in developed countries, coincided with improved living conditions and healthcare. Part of this increase could be ascribed to the lack of exposure to infectious agents like helminths that co-evolved with us and display potent immune regulatory actions. In this review we discussed many investigations, including our own, showing that Trichinella spiralis via its excretory-secretory products attenuate Th1/Th17 immunopathological response in autoimmunity and potentiate the protective Th2 and or regulatory T cell response, acting as an effective induction of tolerogenic dendritic cells (DCs), and probably mimicking the autoantigen in some diseases. A recent discovery of T. spiralis extracellular vesicles (TsEVs) suggested that inducing a complex regulation of the immune response requires simultaneous delivery of different signals in nano-sized packages. Indeed, different artificial nanomedical approaches discussed here suggested that co-delivery of multiple signals via nanoparticles is the most promising strategy for the treatment of autoimmune diseases. Although a long way is ahead of us before we could completely replicate natural nano-delivery systems which are both safe and potent in restoring self-tolerance, a clear path is being opened from a careful examination of parasite-host interactions.