Multiple sclerosis: an infectious syndrome involving Chlamydophila pneumoniae

Stratton, Charles W.; Wheldon, D. B.

doi:10.1016/j.tim.2006.09.002

Cited by 55 publications

(38 citation statements)

References 65 publications

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“…Chlamydial infections are often associated with the development of autoimmune disorders such as reactive arthritis (ReA), atherosclerosis, and others (16,45,46). ReA is strongly correlated with the expression of a particular MHC class I allele, HLA-B27 (47)(48)(49).…”

Section: Discussionmentioning

confidence: 99%

Enhanced Direct Major Histocompatibility Complex Class I Self-Antigen Presentation Induced by Chlamydia Infection

et al. 2016

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The direct major histocompatibility complex (MHC) class I antigen presentation pathway ensures intracellular peptides are displayed at the cellular surface for recognition of infected or transformed cells by CD8 ؉ cytotoxic T lymphocytes. Chlamydia spp. are obligate intracellular bacteria and, as such, should be targeted by CD8 ؉ T cells. It is likely that Chlamydia spp. have evolved mechanisms to avoid the CD8 ؉ killer T cell responses by interfering with MHC class I antigen presentation. Using a model system of self-peptide presentation which allows for posttranslational control of the model protein's stability, we tested the ability of various Chlamydia species to alter direct MHC class I antigen presentation. Infection of the JY lymphoblastoid cell line limited the accumulation of a model host protein and increased presentation of the model-protein-derived peptides. Enhanced selfpeptide presentation was detected only when presentation was restricted to defective ribosomal products, or DRiPs, and total MHC class I levels remained unaltered. Skewed antigen presentation was dependent on a bacterial synthesized component, as evidenced by reversal of the observed phenotype upon preventing bacterial transcription, translation, and the inhibition of bacterial lipooligosaccharide synthesis. These data suggest that Chlamydia spp. have evolved to alter the host antigen presentation machinery to favor presentation of defective and rapidly degraded forms of self-antigen, possibly as a mechanism to diminish the presentation of peptides derived from bacterial proteins.

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Section: Discussionmentioning

confidence: 99%

Enhanced Direct Major Histocompatibility Complex Class I Self-Antigen Presentation Induced by Chlamydia Infection

et al. 2016

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“…It has been suggested for over a decade that microorganisms contribute to the pathogenesis of MS (30)(31)(32)(33)(34)(35). However, findings have not been sufficient to establish an etiological or causal relationship between microbes and neurological inflammation.…”

Section: Microbiota Regulates Pro-and Antiinflammatory Responses In Thementioning

confidence: 99%

Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis

Lee

Menezes

Umesaki

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

1,148

908

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Although the effects of commensal bacteria on intestinal immune development seem to be profound, it remains speculative whether the gut microbiota influences extraintestinal biological functions. Multiple sclerosis (MS) is a devastating autoimmune disease leading to progressive deterioration of neurological function. Although the cause of MS is unknown, microorganisms seem to be important for the onset and/or progression of disease. However, it is unclear how microbial colonization, either symbiotic or infectious, affects autoimmunity. Herein, we investigate a role for the microbiota during the induction of experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Mice maintained under germ-free conditions develop significantly attenuated EAE compared with conventionally colonized mice. Germ-free animals, induced for EAE, produce lower levels of the proinflammatory cytokines IFN-γ and IL-17A in both the intestine and spinal cord but display a reciprocal increase in CD4+ regulatory T cells (Tregs). Mechanistically, we show that gut dendritic cells from germ-free animals are reduced in the ability to stimulate proinflammatory T cell responses. Intestinal colonization with segmented filamentous bacteria (SFB) is known to promote IL-17 production in the gut; here, we show that SFBs also induced IL-17A-producing CD4 + T cells (Th17) in the CNS. Remarkably, germ-free animals harboring SFBs alone developed EAE, showing that gut bacteria can affect neurologic inflammation. These findings reveal that the intestinal microbiota profoundly impacts the balance between pro-and antiinflammatory immune responses during EAE and suggest that modulation of gut bacteria may provide therapeutic targets for extraintestinal inflammatory diseases such as MS.

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“…Indeed, higher rates of C. pneumoniae transcription were found in the cerebrospinal fluid of 84 patients with the more progressive form of MS [66]. These studies strongly support the presence of C. pneumoniae in the brains of MS patients with progressive disease [67,68].…”

Section: Multiple Sclerosis (Ms)mentioning

confidence: 60%

Neurodegenerative and Fatiguing Illnesses, Infections and Mitochondrial Dysfunction: Use of Natural Supplements to Improve Mitochondrial Function.

Nicolson

Settineri

Ellithorpe³

2014

FFHD

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Background: Many chronic diseases and illnesses are associated with one or more chronic infections, dysfunction of mitochondria and reduced production of ATP. This results in fatigue and other symptoms that occur in most if not all chronic conditions and diseases.Methods: This is a review of the published literature on chronic infections in neurodegenerative diseases and fatiguing illnesses that are also typified by mitochondrial dysfunction. This contribution also reviews the use of natural supplements to enhance mitochondrial function and reduce the effects of chronic infections to improve overall function in various chronic illnesses.Results: Mitochondrial function can be enhanced by the use of various natural supplements, notably Lipid Replacement Therapy (LRT) using glyerolphospholipids and other mitochondrial supplements. In various chronic illnesses that are characterized by the presence of chronic infections, such as intracellular bacteria (Mycoplasma, Borrelia, Chlamydia and other infections) and viruses, LRT has proven useful in multiple clinical trials. For example, in clinical studies on chronic fatigue syndrome, fibromyalgia syndrome and other chronic fatiguing illnesses where a large majority of patients have chronic infections, LRT significantly reduced fatigue by 35-43% in different clinical trials and increased mitochondrial function. In clinical trials on patients with multiple intracellular bacterial infections and intractable fatigue LRT plus other mitochondrial supplements significantly decreased fatigue and improved mood and cognition.Conclusions: LRT formulations designed to improve mitochondrial function appear to be useful as non-toxic dietary supplements for reducing fatigue and restoring mitochondrial and other cellular membrane functions in patients with chronic illnesses and multiple chronic infections. BackgroundPatients with chronic neurodegenerative, neurobehavioral and fatiguing illnesses commonly test positive for systemic and central nervous system (CNS) bacterial and viral infections [1][2][3]. In addition, other chronic illnesses where neurological manifestations are routinely found, such as autoimmune diseases and other chronic illnesses and disorders, also show evidence of systemic bacterial and viral infections that could be important in disease inception, progression and/or enhancing the types and severities of signs and symptoms [2,3].Evidence of bacterial infections, such as Mycoplasma species, Chlamydia pneumoniae, Borrelia burgdorferi, among others, and viruses, such as human herpesvirus (HHV), cytomegalovirus (CMV), human herpes viruses (HHV) and other viral infections, have revealed high rates of infection in the illnesses listed above that were not found in control populations [1][2][3]. Although the specific roles of chronic infections in various diseases and their pathogeneses have not been carefully determined, the data suggest that chronic bacterial and/or viral infections are common features of essentially all progressive chronic diseases [1][2][3].An...

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Multiple sclerosis: an infectious syndrome involving Chlamydophila pneumoniae

Cited by 55 publications

References 65 publications

Enhanced Direct Major Histocompatibility Complex Class I Self-Antigen Presentation Induced by Chlamydia Infection

Enhanced Direct Major Histocompatibility Complex Class I Self-Antigen Presentation Induced by Chlamydia Infection

Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis

Neurodegenerative and Fatiguing Illnesses, Infections and Mitochondrial Dysfunction: Use of Natural Supplements to Improve Mitochondrial Function.

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