Modulation of the Inflammatory Signature in an Experimental Autoimmune Encephalomyelitis Model through Treatment with Fasciola hepatica-Derived Recombinant Fatty Acid Binding Protein (rFh15).

Abstract

Background: The observed negative correlation between the geographical distribution of autoimmune diseases and helminth infections points towards a potential role for parasites in the regulation of inflammatory diseases. This phenomenon of immunomodulation is likely attributed to the bioactive molecules found in the excretory-secretory products (ESPs) from helminths. Among these molecules are fatty acid-binding proteins (FABPs), exemplified by the Fasciola hepatica 15 kDa protein (Fh15), which exhibits certain anti-inflammatory properties. In this study, a recombinant variant of Fh15 (rFh15) was produced and subsequently assessed for its anti-inflammatory effects in a murine model of experimental autoimmune encephalomyelitis (EAE).

Methods: EAE was induced in twelve C57BL/6 mice, while six additional mice were maintained as healthy controls (HCs). The EAE-induced mice received intraperitoneal injections of either 100 μg of rFh15 or PBS, administered thrice both before and after EAE induction. Bodyweight and clinical scores were recorded daily. The extent of inflammatory cell infiltration and demyelination in the spinal cord was determined through hematoxylin/eosin, luxol fast blue, and anti-myelin basic protein staining. Splenocytes were isolated, and the expression levels of cytokine genes implicated in inflammation, along with their transcription factors, were quantified via real-time PCR.

Results: Clinical score, lymphocyte infiltration rate, and demyelinated plaques were significantly lower in rFh15-treated EAE mice compared with PBS-treated counterparts. The expression levels of RORγt, IL-17, IL-12, IL-1β, TNF, and IFN-γ genes were significantly reduced, and the expression rates of GATA3, IL-4, FOXP3, and IL-10 genes were significantly increased in the rFh15- treated EAE mice compared with PBS-treated group.

Conclusion: The anti-inflammatory effects of rFh15 suggest that it could be further evaluated and applied in autoimmune disorders as a safe helminth therapy component.