Helminth Products Potently Modulate Experimental Autoimmune Encephalomyelitis by Downregulating Neuroinflammation and Promoting a Suppressive Microenvironment

Abstract

A negative correlation between the geographical distribution of autoimmune diseases and helminth infections has been largely associated in the last few years with a possible role for such type of parasites in the regulation of inflammatory diseases, suggesting new pathways for drug development. However, few helminth-derived immunomodulators have been tested in experimental autoimmune encephalomyelitis (EAE), an animal model of the human disease multiple sclerosis (MS). The immunomodulatory activities of Taenia crassiceps excreted/secreted products (TcES) that may suppress EAE development were sought for. Interestingly, it was discovered that TcES was able to suppress EAE development with more potency than dexamethasone; moreover, TcES treatment was still effective even when inoculated at later stages after the onset of EAE. Importantly, the TcES treatment was able to induce a range of Th2-type cytokines, while suppressing Th1 and Th17 responses. Both the polyclonal and the antigen-specific proliferative responses of lymphocytes were also inhibited in EAE-ill mice receiving TcES in association with a potent recruitment of suppressor cell populations. Peritoneal inoculation of TcES was able to direct the normal inflammatory cell traffic to the site of injection, thus modulating CNS infiltration, which may work along with Th2 immune polarization and lymphocyte activation impairment to downregulate EAE development.

Interleukin-5 Mediates Parasite-Induced Protection against Experimental Autoimmune Encephalomyelitis: Association with Induction of Antigen-Specific CD4+CD25+ T Regulatory Cells

“…IL-33 enhances both Th2 effector responses and activation of Treg by Type-2 cytokines ( 73 , 74 ), thus these findings may complement those described here. Other immune regulatory mechanisms may be induced by type-2 responses, including alternate activated macrophages (M2), which are induced when parasite infection reduces severity of EAE ( 32 ).…”

“…Spontaneous recovery from EAE is associated with activation of Treg that promote recovery ( 29 , 30 ). Parasitic infections reduce severity of EAE, including Th17 response and T cell infiltration to central nervous system (CNS) ( 31 , 32 ). Parasitic infections that reduce severity of EAE and induce Treg include Trypanosoma cruzi ( 33 ), Plasmodium chaubaudi ( 34 ), Trichinella spiralis ( 35 ), and Nippostrongylus brasiliensis ( 36 ).…”

The Helminth Parasite Heligmosomoides polygyrus Attenuates EAE in an IL-4Rα-Dependent Manner

“…However, in the current study we found HES was only able to delay disease onset indicating that the immunological changes produced by HES were not strong enough to recapitulate the effect seen with live parasite infection. In contrast, a study with Taenia crassiceps ES (TcES), which showed that in addition to Th2-deviation, ES was able to sequester inflammatory cells into the periphery and therefore inhibit the induction of EAE by preventing trafficking of cells to the CNS ( 43 ), a mechanism that could well underpin the protective ability of live H. polygyrus . Soluble egg antigens (SEA) from S. japonicum and T. spiralis ES also ameliorate EAE disease in a way that was similar to whole parasite infection, protection that was related to a Th2 shift in both the periphery and CNS ( 19 , 44 ).…”

Janus-Faced Myeloid-Derived Suppressor Cell Exosomes for the Good and the Bad in Cancer and Autoimmune Disease

“…Notably, SADBE treatment can be replaced by the transfer of MDSC ( 262 ). In EAE, it was demonstrated that helminth products stimulate the production of TH2 cytokines and suppress TH1 and TH17 responses, the therapeutic efficacy exceeding that of corticosteroid treatment ( 263 ). Another option are statins, which are cholesterol lowering drugs, also described to induce immunosuppression.…”