Galectin isolated from parasite inhibits remission of experimental autoimmune encephalomyelitis by up-regulating autoantibody

Abstract

SummaryRecently, parasite infections or parasite-derived products have been suggested as a therapeutic strategy with suppression of immunopathology, which involves the induction of regulatory T cells or/and T helper type 2 (Th2) responses. In a recent study, researchers reported that constructed recombinant galectin (rTl-gal) isolated from an adult worm of the gastrointestinal nematode parasite Toxascaris leonina attenuated clinical symptoms of inflammatory bowel disease in mice treated with dextran sulphate sodium. Noting the role of rTl-gal in inflammatory disease, we attempted to investigate the effect of the parasite via its rTl-gal on neuronal autoimmune disease using experimental autoimmune encephalomyelitis (EAE), a mouse inflammatory and demyelinating autoimmune disease model of human multiple sclerosis. In this model, rTl-gal-treated experimental autoimmune encephalomyelitis (EAE) mice failed to recover after the peak of the disease, leading to persistent central nervous system (CNS) damage, such as demyelination, gliosis and axonal damage. Further, rTl-gal-treated EAE mice markedly increased the number of CD45R/B220 1 B cells in both infiltrated inflammation and the periphery, along with the increased production of autoantibody [antimyelin oligodendrocyte glycoprotein (MOG) ] in serum at chronic stage. Upon antigen restimulation, rTl-gal treatment affected the release of overall cytokines, especially interferon (IFN)-g and tumour necrosis factor (TNF)-a. Our results suggest that galectin isolated from a gastrointestinal parasite can deliver a harmful effect to EAE contrary to its beneficial effect on inflammatory bowel disease.

Galectins - Important players of the immune response to CNS parasitic infection

“…Administration of Tl-gal to EAE mice increased the number of CD45R/B2201 B cells and production of autoantibody [anti-myelin oligodendrocyte glycoprotein (MOG)35–55] in serum at the chronic stage with changes in cytokine TNF-α and IFN-γ in spleen cells. Unexpectedly, despite the similarly of parasitic Tl-gal to human Gal-9, the proteins exhibit dissimilar influences on EAE course, which can indicate different functions of nematode and host galectin ( Bing et al., 2015 ) or possibly their competitive effects.…”

A critical analysis of helminth immunotherapy in multiple sclerosis

“…This includes dosage and timing of inoculation with larvae, ova, or excreted-secreted (E/S) products from 12 different helminthic species, and adoptive transfer of leukocytes treated with E/S products or isolated from helminth-infected animals into mice or rats prior to or after EAE immunization (Figure 1, Table 1). 13–35…”

“…36 Only one study reported detrimental effects of HIT: treatment of Toxascaris leonina -derived galectin following EAE immunization prevented remission of EAE-induced paralytic symptoms. 34…”

The roles of galectins in parasitic infections

“…The clinical symptoms of DSS-treated mice after pre-treatment with rTl-gal were less profound than those of untreated group (Kim et al, 2010). However, in an experimental autoimmune encephalomyelitis model, rTl-gal exhibited a function distinct from that of Gal-9 and aggravated disease severity by enhancing the production of pathogenic autoantibody and proinflammatory cytokines (Th2 response) (Bing et al, 2015).…”