Modulation of experimental autoimmune encephalomyelitis through colonisation of the gut with Escherichia coli

2020 ◽  
pp. 1-16 ◽  
Author(s):  
J.E. Libbey ◽  
J.M.S. Sanchez ◽  
B.A. Fleming ◽  
D.J. Doty ◽  
A.B. DePaula-Silva ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Gut Microbiota ◽  
Disease Onset ◽  
Probiotic Bacterium ◽  
Coli Strain ◽  
Preclinical Model ◽  
Autoimmune Encephalomyelitis ◽  
Cns Inflammation ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is a neuro-inflammatory autoimmune disease of the central nervous system (CNS) that affects young adults. It is characterised by the development of demyelinating lesions and inflammation within the CNS. Although the causes of MS are still elusive, recent work using patient samples and experimental animal models has demonstrated a strong relationship between the gut microbiota and its contribution to CNS inflammation and MS. While there is no cure for MS, alteration of the gut microbiota composition through the use of probiotics is a very promising treatment. However, while most recent works have focused on the use of probiotics to modify pre-existing disease, little is known about its role in protecting from the establishment of MS. In this study, we determined whether colonisation with the probiotic bacterium Escherichia coli strain Nissle 1917 (EcN) could be used as a prophylactic strategy to prevent or alter the development of experimental autoimmune encephalomyelitis (EAE), a preclinical model of MS. We found that double gavage (two doses) of EcN before induction of EAE delayed disease onset and decreased disease severity. We also found that EcN-treated mice had decreased amounts of perivascular cuffing, CD4+ T cell infiltration into the CNS, together with significantly decreased absolute numbers of Th1 cells, and reduced activation of microglia. Although further studies are necessary to comprehend the exact protective mechanisms induced, our study supports a promising use of EcN as a probiotic for the prevention of MS.

scholarly journals Constipation induced gut microbiota dysbiosis exacerbates experimental autoimmune encephalomyelitis in C57BL/6 mice

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiuli Lin ◽  
Yingying Liu ◽  
Lili Ma ◽  
Xiaomeng Ma ◽  
Liping Shen ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Gut Microbiota ◽  
Blood Brain Barrier ◽  
Intestinal Barrier ◽  
Brain Barrier ◽  
Autoimmune Encephalomyelitis ◽  
Gm Csf ◽  
Blood Brain ◽  
Gut Microbiota Dysbiosis ◽  
Experimental Autoimmune

Abstract Background Constipation is a common gastrointestinal dysfunction which has a potential impact on people's immune state and their quality of life. Here we investigated the effects of constipation on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Methods Constipation was induced by loperamide in female C57BL/6 mice. The alternations of gut microbiota, permeability of intestinal barrier and blood–brain barrier, and histopathology of colon were assessed after constipation induction. EAE was induced in the constipation mice. Fecal microbiota transplantation (FMT) was performed from constipation mice into microbiota-depleted mice. Clinical scores, histopathology of inflammation and demyelination, Treg/Th17 and Treg17/Teff17 imbalance both in the peripheral lymphatic organs and central nervous system, cytokines include TGF-β, GM-CSF, IL-10, IL-17A, IL-17F, IL-21, IL-22, and IL-23 in serum were assessed in different groups. Results Compared with the vehicle group, the constipation mice showed gut microbiota dysbiosis, colon inflammation and injury, and increased permeability of intestinal barrier and blood–brain barrier. We found that the clinical and pathological scores of the constipation EAE mice were severer than that of the EAE mice. Compared with the EAE mice, the constipation EAE mice showed reduced percentage of Treg and Treg17 cells, increased percentage of Th17 and Teff17 cells, and decreased ratio of Treg/Th17 and Treg17/Teff17 in the spleen, inguinal lymph nodes, brain, and spinal cord. Moreover, the serum levels of TGF-β, IL-10, and IL-21 were decreased while the GM-CSF, IL-17A, IL-17F, IL-22, and IL-23 were increased in the constipation EAE mice. In addition, these pathological processes could be transferred via their gut microbiota. Conclusions Our results verified that constipation induced gut microbiota dysbiosis exacerbated EAE via aggravating Treg/Th17 and Treg17/Teff17 imbalance and cytokines disturbance in C57BL/6 mice.

scholarly journals Inhibitory Effect of Matrine on Blood-Brain Barrier Disruption for the Treatment of Experimental Autoimmune Encephalomyelitis

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Su Zhang ◽  
Quan-Cheng Kan ◽  
Yuming Xu ◽  
Guang-Xian Zhang ◽  
Lin Zhu
Keyword(s):  
Basement Membrane ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Blood Brain Barrier ◽  
Adaptor Protein ◽  
Brain Barrier ◽  
Autoimmune Encephalomyelitis ◽  
Novel Therapy ◽  
Cns Inflammation ◽  
Blood Brain ◽  
Experimental Autoimmune

Dysfunction of the blood-brain barrier (BBB) is a primary characteristic of experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS). Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flave, has been recently found to suppress clinical EAE and CNS inflammation. However, whether this effect of MAT is through protecting the integrity and function of the BBB is not known. In the present study, we show that MAT treatment had a therapeutic effect comparable to dexamethasone (DEX) in EAE rats, with reduced Evans Blue extravasation, increased expression of collagen IV, the major component of the basement membrane, and the structure of tight junction (TJ) adaptor protein Zonula occludens-1 (ZO-1). Furthermore, MAT treatment attenuated expression of matrix metalloproteinase-9 and -2 (MMP-9/-2), while it increased the expression of tissue inhibitors of metalloproteinase-1 and -2 (TIMP-1/-2). Our findings demonstrate that MAT reduces BBB leakage by strengthening basement membrane, inhibiting activities of MMP-2 and -9, and upregulating their inhibitors. Taken together, our results identify a novel mechanism underlying the effect of MAT, a natural compound that could be a novel therapy for MS.

scholarly journals Gut Microbiota Confers Resistance of Albino Oxford Rats to the Induction of Experimental Autoimmune Encephalomyelitis

2018 ◽  
Vol 9 ◽  
Author(s):  
Suzana Stanisavljević ◽  
Miroslav Dinić ◽  
Bojan Jevtić ◽  
Neda Đedović ◽  
Miljana Momčilović ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Gut Microbiota ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

scholarly journals Modification of the Disease Progression in Mice with Experimental Autoimmune Encephalomyelitis Using Anti-Mitotic Compounds

2021 ◽  
Author(s):  
◽  
Kevin Patrick Crume
Keyword(s):  
Nitric Oxide ◽  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Disease Onset ◽  
Autoimmune Response ◽  
Peloruside A ◽  
Proliferating Cells ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

<p>Multiple sclerosis (MS) is a multi-faceted disease, and is believed to be caused by an autoimmune response to myelin antigens in the central nervous system. Experimental autoimmune encephalomyelitis (EAE), an animal model for MS. manifests itself in various forms that parallel many aspects of MS, including the appearance of symptoms, initiation events, and pathophysiology. The hallmark of any immune response is the antigen-specific proliferation of immune cells, and during the initiation events of EAE, proliferating CD4+ T cells are the primary mediators of disease. This thesis explores if targeting these proliferating cells with the anti-mitotic compounds paclitaxel and peloruside A can delay or prevent the unset of EAE, thus providing a novel therapeutic avenue for MS research. The anti-cancer compound, paclitaxel, is an anti-mitotic drug that prevents microtubule depolymerisation. Although paclitaxel has been used in the clinical setting to treat cancer for over a decade, it has been determined that paclitaxel stimulates murine toll-like receptor 4 (TLR4) complex, which is the major LPS receptor. A novel microtubule-stabilising compound, peloruside, is currently subject to intensive investigations due to its functional similarity to paclitaxel. The results from this project found that peloruside and paclitaxel inhibited the proliferation of mitogen-stimulated splenocytes with IC50 values of 83 nM and 30 nM, respectively, but did not affect the viability of non-proliferating cells In contrast to paclitaxel, peloruside did not cause the TLR4-mediated production of the inflammatory mediators. TNF-epsilon, IL-12, and nitric oxide, when cultured with IFN-epsilon stimulated murine macrophages. Interestingly, when LPS was included with either paclitaxel or peloruside A, both drugs decreased the production of TNF-e and nitric oxide from macrophages, suggesting that microtubule-stabilising compounds may have anti-inflammatory effects. To identify any immunomodifying effects of paclitaxel in vivo, paclitaxel was administered to mice that were immunised with the myelin protein MOG in complete Freund's adjuvant (CFA) to induce EAE. When Taxol was administered to mice for 5 consecutive days immediately following CFA/MOG immunisation, the onset of EAE was delayed by approximately I week. Moreover, the administration of peloruside following the same treatment regime also resulted in a similar delay of disease onset. Taxol treatments, however, lead to significant mortality in immunised, but not unimmunised mice. Interestingly, although Taxol is an anti-mitotic drug, the proliferation of antigen-specific T cells was not inhibited in vivo by the Taxol treatment. The findings revealed in this thesis present an opportunity to pursue a new avenue of research for the therapeutic treatment of MS sufferers, and possibly other inflammatory autoimmune disorders.</p>

scholarly journals The direct deleterious effect of Th17 cells in the nervous system compartment in multiple sclerosis and experimental autoimmune encephalomyelitis: one possible link between neuroinflammation and neurodegeneration

2020 ◽  
Vol 28 (1) ◽  
pp. 9-17 ◽  
Author(s):  
Rodica Balasa ◽  
Smaranda Maier ◽  
Laura Barcutean ◽  
Adina Stoian ◽  
Anca Motataianu
Keyword(s):  
Multiple Sclerosis ◽  
Nervous System ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Th17 Cells ◽  
Direct Interaction ◽  
Autoimmune Encephalomyelitis ◽  
Cns Inflammation ◽  
Direct Role ◽  
Autoimmune Attack ◽  
Experimental Autoimmune

AbstractThe processes of demyelination and neurodegeneration in the central nervous system (CNS) of multiple sclerosis (MS) patients and experimental autoimmune encephalomyelitis (EAE) are secondary to numerous pathophysiological mechanisms. One of the main cellular players is the Th17 lymphocyte. One of the major functions described for Th17 cells is the upregulation of pro-inflammatory cytokines, such as IL-17 at the level of peripheral and CNS inflammation. This review will focus on the newly described and unexpected, direct role played by the Th17 cells in the CNS of MS patients and EAE models. Th17 and their main cytokine, IL-17, are actively involved in the onset and maintenance of the immune cascade in the CNS compartment as Th17 were found to achieve brain-homing potential. Direct interaction of myelin oligodendrocyte glycoprotein - specific Th17 with the neuronal cells firstly induces demyelination and secondly, extensive axonal damage. The Th17 cells promote an inflammatory B cell response beyond the BBB through the presence of infiltrating Th follicles. Due to their role in preventing remyelination and direct neurotoxic effect, Th17 cells might stand for an important connection between neuroinflammation and neurodegeneration in a devastating disease like MS. The Th17 cell populations have different mechanisms of provoking an autoimmune attack not only in the periphery but also in the CNS of MS patients.

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