Infection of non-encapsulated species of Trichinella ameliorates experimental autoimmune encephalomyelitis involving suppression of Th17 and Th1 response

Abstract

Epidemiological and experimental studies have indicated that helminth infections can ameliorate autoimmune diseases. The present study investigated the amelioration effect of the Trichinella pseudospiralis infection on experimental autoimmune encephalomyelitis (EAE), a T-cell-mediated autoimmune disease of central nervous system (CNS), and expression kinetics of Th17 and Th1 cytokine which play a crucial role in the pathogenesis of EAE. The results indicated that the infection of helminth T. pseudospiralis obviously ameliorated clinical severity and greatly delayed the onset of EAE induced by myelin oligodendrocyte glycoprotein (MOG) immunization. Infection caused much lesser inflammatory infiltration and demyilination in the CNS of infected EAE mice than uninfected EAE mice. The reduced infiltration was also suggested by the expressions of the inflammation cytokines, IL-17, IL-6, IL-1β, IFN-γ, and TNF-α, which were high in the spinal cords of the uninfected EAE mice, but was nearly normal or low in the infected EAE mice. The increased production of MOG-induced IL-17 and IFN-γ and the expression of IL-6, IL-1β, TGF-β in splenocytes after restimulation with MOG was inhibited in the infected EAE mice. On the other hand, the greatly induced Th2 response was observed in the splenocytes of the infected EAE mice. The present study showed that T. pseudospiralis infection can suppresses EAE by reducing the inflammatory infiltration in CNS, likely associated with the suppression of Th17 and Th1 responses by the infection.

Excretory/Secretory Products from Trichinella spiralis Adult Worms Ameliorate DSS-Induced Colitis in Mice

“…Trichinella infections have been found to down-regulate the inflammatory immunopathology caused by autoimmune diseases in various animal models such as experimental autoimmune encephalomyelitis (EAE) in rats [11], [43], [60], [61] and experimental colitis in mice [38], [39]. However, the mechanism or the molecules involved in this immunomodulation are not quite known.…”

“…The ES proteins from T. spiralis muscle larvae (MES) have shown to be able to stimulate bone-marrow derived dendritic cells (DCs) to produce a mixed Th1/Th2 cytokine profile with the predominance of Th2 and regulatory cytokines [29]. Mice received T. spiralis MES simulated DCs significantly boosted Treg cells that secreted regulatory IL-10 and TGF-β cytokines [62], and decreased production of IFN-γ and IL-17 that leaded to the amelioration of experimental autoimmune encephalomyelitis [60], [61]. Except for MES, Trichinella AES was also able to inhibit pro-inflammatory cytokines and induce regulatory cytokines such as IL-10 and TGF-β via macrophage cells in vitro [29], [32], suggesting AES also plays similar roles in regulating immunological disorders.…”

“…It benefits the helminths to survive the host Th1-mediated cellular attack, simultaneously preventing the host's immune system from overreacting to innate or external immunogens or allergens [7], [23]. Th17 is another subset of CD4 T cells that produce IL-17, a pro-inflammatory cytokine involved in the autoimmune diseases and other immunopathology [61], [68]. In this study, we have observed the high level of pro-inflammatory cytokines (IFN-γ, IL-6 and IL-17) produced by lymphocytes from spleen, MLN or colon of mice with DSS-induced colitis, further suggesting these pro-inflammatory cytokines are involved in the inflammation of colitis.…”

Parasitic Helminths as Potential Therapeutic Agents Against Autoimmune Disorders

“…According to Sewell et al (2003), the intra-peritoneal injection of schistosome eggs protected mice from EAE, whereas La Flamme et al (2003), reported that a similar injection did not have protective effect. In general, a down-regulation of both Th17 and Th1 cytokine expression has been demonstrated (Walsh et al, 2009;Wu et al, 2010;Reyes et al, 2011) except in papers published before the emergence of the Th17 concept (Sewell et al, 2003;La Flamme et al, 2003). Regarding cellular involvement in the suppression, B cells highly expressing CD23 were shown to be responsible for EAE suppression in adoptive transfer experiments.…”

Nonencapsulated Trichinella pseudospiralis Infection Impairs Follicular Helper T Cell Differentiation with Subclass-Selective Decreases in Antibody Responses

“…Moreover, Aranzamendi et al reported that Trichinella infection protected the host against allergic airway inflammation (8). It is obvious that Trichinella infection affects the host immune responses, but most studies regarding immunomodulatory actions by Trichinella were done using T. spiralis, and studies of immunomodulation by T. pseudospiralis are available in limited numbers only (9). As the immunomodulatory activity of T. pseudospiralis may be different from that of T. spiralis as mentioned above, it is necessary to make clear the mechanisms underlying the immunomodulation by T. pseudospiralis.…”