New delivery system for Trichinella spiralis antigens - accelerated approach to autoimmunity treatment

Abstract

Trichinella spiralis possess the potential to induce tolerance and restrain excessive immune responses, thus exerting beneficial effect on the outcome of experimental autoimmune encephalomyelitis (EAE), the animal model of human disease multiple sclerosis. Trichinella achieves this by continuous release of its excretoysecretory (ES L1) products in the form of a complex mixture of individual components and extracellular vesicles (TsEVs), preferentially exsosomes. Our previous results suggested that the complex modulation of the host immune response is achieved by ES L1 products or its individula components, which induce the maturation of dendritic cells towards tolerogenic status. A new delivery system, based on nanomaterials as carriers of ES L1, was designed to resemble what happens in nature, ie. spontaneous release of Trichinella products over an extended period of time using a less invasive route of administration than all previously described for the treatment of autoimmune diseases. PLGA biodegradable nanofibers loaded with ES L1 (PLGA-ES L1), were used as subcutaneous implants. The tretment proved to be safe with no side effects, successful in delivering parasite products and mitigating the course of relapsing/remitting EAE in Dark Agouti rats. The mechanisms we examined included events at the systemic level and target tissue, spinal cord, that explain the shift from the pro- to anti-inflammatory responses and success of treatment. PLGA-ES L1 treatment also prevents the EAEinduced disruption of intestinal epithelial barrier. It diminished the inflammation by lowering the expression of TNF-α in gastrointestinal tract (GIT) and succesfully maintain the expression of mRNA for claudin, the most important tight junction protein in GIT. Obseved protective effect was acompained with the re-establishment of gut microbiota diversity that was disturbed in EAE-induced animals.