Lymphatic system and gut microbiota affect immunopathology of neuroinflammatory diseases, including multiple sclerosis, neuromyelitis optica and Alzheimer's disease

Abstract

Microbial infections lead to neurological damages either by direct infection in the nervous tissues or by uncontrolled immune responses (immunopathology). For example, in Zika virus infection, microcephaly can be caused by the former, i.e., direct viral infection in the brain, while Guillain-Barré syndrome (GBS) seems to be antibody-mediated immunopathology. Although a variety of factors affect immunopathology, two essential systems maintaining whole-body homeostasis had long been neglected: 1) the lymphatic system and 2) microbiota. Only recently, the role of the lymphatic system in immunopathology is beginning to be clarified. During infection, increased lymphatic flow limits edema and prevent tissue dendritic cell retention, while lymphostasis can lead to chronic inflammation. The role of gut microbiota, particularly bacterial community, in immunopathology has also been clarified recently; “bad bacteria” are proposed to exacerbate any immunopathology. For example, Helicobacter pylori is associated with not only gastritis but also extra-intestinal diseases, including neuromyelitis optica (NMO) and Alzheimer’s disease. However, H. pylori and another bad bacterium Clostridium perfringens type A have been proposed to be protective against multiple sclerosis (MS). The above discrepancy on the roles of microbiota can be attributed to several conflicting factors, such as oversimplification, methodology, and taxonomy, which are summarized as “10 pitfalls of microbiota studies.”

Facets of Theiler’s Murine Encephalomyelitis Virus-Induced Diseases: An Update

“…Experimental intracerebral infection of young adult mice causes flaccid paralysis of the hind limbs [3,7]. The course of Theiler’s murine encephalitis (TME) depends on the virus and mouse strains as well as other factors including intestinal microbiota and stress [3,14,15,16,17]. Mice develop an acute polioencephalomyelitis within two weeks following experimental intracerebral TMEV infection.…”

Gut-Induced Inflammation during Development May Compromise the Blood-Brain Barrier and Predispose to Autism Spectrum Disorder

“…It was found that the ablation of intestinal lacteals disrupted blood vessel and villous architecture, which lead to increased invasion of intestinal pathogens into the circulatory system [ 80 ]. Indeed, common disease states like IBS and IBD have been shown to reduce the functionality of lymphatic vessels as well [ 81 , 82 ]. As discussed previously, this, therefore, may induce systemic inflammation and subsequent neuroinflammation.…”

Bioinformatics Analysis of Gut Microbiota and CNS Transcriptome in Virus-Induced Acute Myelitis and Chronic Inflammatory Demyelination; Potential Association of Distinct Bacteria With CNS IgA Upregulation

“…When the activation of the immune system is appropriate, this contributes to the elimination/regulation of microbes. Dysbiosis, an altered state of bacterial community, has been associated with health conditions and diseases ( 16 , 17 ). Dysbiosis could lead to excessive activation of the immune system; uncontrolled immune responses can cause immunopathology, particularly in the gastrointestinal tract.…”