Chronic Toxoplasma gondii Infection Alleviates Experimental Autoimmune Encephalomyelitis by the Immune Regulation Induci
- PDF / 1,668,969 Bytes
- 18 Pages / 595.276 x 790.866 pts Page_size
- 62 Downloads / 161 Views
ORIGINAL ARTICLE
Chronic Toxoplasma gondii Infection Alleviates Experimental Autoimmune Encephalomyelitis by the Immune Regulation Inducing Reduction in IL-17A/Th17 Via Upregulation of SOCS3 Do-Won Ham 1 & Sang-Gyun Kim 1 & Seung-Hwan Seo 1 & Ji-Hun Shin 1 & Sang Hyung Lee 2 & Eun-Hee Shin 1,3 Accepted: 21 October 2020 # The Author(s) 2020
Abstract Experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis (MS), a demyelinating autoimmune disease caused by the infiltration of a harmful autoreactive Th1 and Th17 cells. To mitigate MS, which is impossible to cure with medication only, immunomodulatory interventions that prevent Th17 cell activation are ideal. The objective of the present study was to analyze the effect of Toxoplasma gondii infection on the onset of EAE. Our results found that Toxoplasma gondii infection in the brain increases SOCS3 expression and decreases the phosphorylation of STAT3, resulting in reducing IL-17A and IL-23, which suppress the differentiation and expansion of pathogenic Th17 cells, an important factor in MS development. These immune responses resulted in a reduction in the clinical scoring of EAE induced by myelin oligodendrocyte glycoprotein 35– 55 immunization. In the EAE group with T. gondii infection (Tg + EAE group), Th17-related immune responses that exacerbate the onset of EAE were reduced compared to those in the EAE group. This study suggests that the alleviation of EAE after T. gondii infection is regulated in a SOCS3/STAT3/IL-17A/blood–brain barrier integrity-dependent manner. Although parasite infection would not be permitted for MS treatment, this study using T. gondii infection identified potential targets that contribute to disease attenuation. Key Words Toxoplasma gondii infection . EAE . SOCS3 . Th17 . IL-17A . STAT3 . immune regulation . autoimmunity
Introduction Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) and the most common inflammatory neurological disease in young adults [5, 21]. The mean age of diagnosis is approximately 30 years
* Sang Hyung Lee [email protected] * Eun-Hee Shin [email protected] 1
Department of Tropical Medicine and Parasitology, Seoul National University College of Medicine, and Institute of Endemic Diseases, Seoul 03080, Republic of Korea
2
Department of Neurosurgery, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul 07061, Republic of Korea
3
Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea
with most patients presenting with periodic neurological relapses [21]. One to two decades after onset, many patients with MS enter the progressive phase of the disease, but nevertheless, the underlying cause of this disease remains elusive [21]. Common neurological manifestations of MS include optic neuritis, diplopia, sensory loss, limb weakness, gait ataxia, and cognitive dysfunction [5, 21]. Main causes of MS development are demyelination, wherein the myelin sheath or the oligodendrocyte cell body
Data Loading...
