Oral Tolerance Induction in Experimental Autoimmune Encephalomyelitis with Candida utilis Expressing the Immunogenic MOG35-55 Peptide

Abstract

Multiple sclerosis (MS) is an autoimmune disease that attacks myelinated axons in the central nervous system. Induction of oral tolerance is a potent mechanism to prevent autoimmunity. The food yeast Candida utilis was used to test the therapeutic potential of oral tolerance induction in an animal model of human multiple sclerosis (MS). We constructed a C. utilis strain, which displays a fusion peptide composed of the encephalitogenic MOG35-55 peptide and the C. utilis Gas1 cell wall protein on its surface.By immunizing mice with MOG35-55 peptide experimental autoimmune encephalomyelitis (EAE) was induced in a mouse model. Feeding of mice with C. utilis that expresses MOG35-55 peptide on its surface was started seven days prior to immunization and was continued for ten days. Control animals were treated with wild-type fungus or left untreated. Untreated mice developed first clinical symptoms ten days post immunization (p. i.) with an ascending paralysis reaching maximal clinical disability at day 18 to 20 p. i.. Treatment with the wild-type strain demonstrated comparable clinical symptoms. In contrast, oral gavage of MOG35-55-presenting fungus ameliorated the development of EAE. In addition, incidence as well as maximal clinical disease severity were significantly reduced. Interestingly, reduction of disease severity also occurred in animals treated with heat-inactivated C. utilis cells indicating that tolerance induction was independent of fungal viability. Better disease outcome correlated with reduced demyelination and cellular inflammation in the spinal cord, lower T cell proliferation against rechallenge with MOG35-55 and more regulatory T cells in the lymph nodes. Our data demonstrate successful that using the food approved fungus C. utilis presenting the immunogenic MOG35-55 peptide on its surface induced an oral tolerance against this epitope in EAE. Further studies will reveal the nature and extent of an anti-inflammatory environment established by the treatment that prevents the development of an autoimmune disorder affecting the CNS.

Streptococcus thermophilus ST285 Alters Pro-Inflammatory to Anti-Inflammatory Cytokine Secretion against Multiple Sclerosis Peptide in Mice

“…Experimental autoimmune encephalomyelitis (EAE) is an animal model of human MS that has been used to study the effects of probiotic bacteria on CNS [11,12]. One of the safe and appropriate ways to modulate T cells in MS is to orally administer specific autoantigens [13,14]. Administration of Bifidobacteria or Lactobacteria probiotic strains to mice has been shown to increase Treg cells and tumor growth factor (TGF)-β levels and reduce the severity of EAE clinical symptoms, in parallel with improvement in the regeneration of myelin in the spinal cord compared to the control [15,16].…”

MuSK EAMG: Immunological Characterization and Suppression by Induction of Oral Tolerance

“…Oral tolerance has an impact on the numbers and function of Treg cells, on the secretion of pro and anti-inflammatory cytokines and on Th-1/Th-2 effector cells (25). This observation led to attempts to regulate many autoimmune diseases by induction of mucosal tolerance to auto antigens (10,(26)(27)(28). We have previously shown that EAMG was prevented in rats by oral or nasal administration of AChR-derived recombinant fragments when treatment started prior immunization, moreover, ongoing disease was suppressed when mucosal tolerance treatment started at the acute or chronic phase of the disease (11,29).…”

Expanding the Knowledge on the Skillful Yeast Cyberlindnera jadinii

“…Upon this, they are translocated to antigen-presenting cells of Peyer’s plaques or to other lymphoid tissue connected with the gastrointestinal tract [ 74 , 75 ]. The ingestion of engineered C. jadinii cells, carrying a myelin oligodendrocyte glycoprotein antigen on its surface, promoted tolerance to self-antigens in a mouse model of the autoimmune multiple sclerosis (MS) disease [ 76 ]. C. jadinii cells expressing the immunodominant MOG 35–55 epitope of a myelin protein on their surface, fused with the native fungal Gas1 cell wall protein, prevented the typical MS symptoms in this animal model [ 76 ].…”