- Title
- Effects of Chlamydia infection on immune responses in the central nervous system and in multiple sclerosis
- Creator
- Lopez, Nia
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2022
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Multiple sclerosis is a devastating autoimmune disease for which there is no cure. It is caused by our body’s own immune system targeting myelin proteins that surround nerve cells in the CNS for destruction, which results in a loss of neuronal function that causes the symptoms of the disease, such as paralysis. It is unknown why the immune system targets myelin proteins in patients with MS. However, strong evidence suggests that environmental triggers may abnormally activate immune responses in the CNS (which is normally an immune response-free zone) that mistakenly result in autoimmunity against myelin proteins. A greater understanding of immunological causes is required to highlight improved prevention/treatments. Chlamydia pneumoniae is an obligate intracellular Gram-negative bacterium that commonly causes acute respiratory disease in humans. Studies suggest the involvement of Chlamydia in a broad spectrum of diseases ranging from Asthma, Chronic obstructive pulmonary disease, Atherosclerosis, Alzheimer’s disease and MS. Chlamydia infections have been linked with MS, but the nature of this association and whether infections can be targeted to prevent/treat the disease are unknown. In Chapters 2 and 3, I assessed whether Chlamydia could enter and/or induce immune responses in the CNS to determine how infection may affect the disease. I used mouse models-BALB/c and C57BL/6 mice that have differential susceptibility to Chlamydia infection. While BALB/c mice are susceptible to Chlamydia lung infection, C57BL/6 mice are relatively resistant to infection. Importantly, Chlamydia infection of the CNS is characterized by elevated levels of cytokines and chemokine mRNAs (e.g., CXCL10, CXCL9), activation of microglia and astrocytes, and infiltration of CD4+ and CD8+ lymphocytes and macrophages. Although the presence of Chlamydia as assessed by 16S expression was evident in both strains, a higher magnitude of infection and increased influx of immune cells following infection was observed in the CNS of C57BL/6 mice compared to BALB/c mice which may also facilitate an environment for the breaking of tolerance (i.e., inducing autoimmunity) to myelin proteins. Determining how Chlamydia affects the development and/or exacerbation of MS may provide valuable insight into the mechanisms of pathogenesis of disease and, therefore, help identify new targets for novel therapeutic strategies. In order to demonstrate how/whether infections might affect MS, I superimposed murine Chlamydia lung infection on mouse models of MS, Experimental Autoimmune Encephalomyelitis (EAE) in Chapter 03. I investigated how Chlamydia infection affects key immune processes in the CNS and in MS using susceptible EAE mouse model-C57BL/6 and resistant BALB/c model. Importantly, once inside the CNS, I show that Chlamydia infection induces immune responses that are important in the induction of immune responses against myelin which results in earlier and more severe EAE signs/symptoms. Moreover, my studies show that Chlamydia infection enters the CNS (as evidenced by 16S expression in the CNS) and exacerbates key immune responses that worsen key features of MS. To corroborate my findings in mouse models, I also conducted a study on a small cohort of patients with MS to explore the links between Chlamydia infection and MS using ELISA. In conclusion, I found that Chlamydia infection alone caused peripheral immune cell infiltration of the CNS. I also report that Chlamydia lung infection can promote or facilitate an inflammatory environment that influences the incidence and severity of EAE/MS.
- Subject
- Chlamydia infection; immune responses; multiple sclerosis; central nervous system
- Identifier
- http://hdl.handle.net/1959.13/1512316
- Identifier
- uon:56605
- Rights
- Copyright 2022 Nia Lopez
- Language
- eng
- Full Text
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| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT01 | Thesis | 6 MB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Abstract | 419 KB | Adobe Acrobat PDF | View Details Download |