The influence of common infections on clinical course and neurodegeneration in an animal model of multiple sclerosis

by Prateek Kumar
Doctoral thesis
Date of Examination:2014-09-07
Date of issue:2015-03-05
Advisor:Prof. Dr. Mathias Bähr
Referee:Prof. Dr. Mikael Simons
Referee:Prof. Dr. Klaus-Armin Nave
Persistent Address: http://dx.doi.org/10.53846/goediss-4967

 

 

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Abstract

English

The course of Multiple Sclerosis (MS), a chronic autoimmune disease, can be influenced by systemic infections. The common notion is that bacterial infections worsen disease symptoms and lead to enhanced neurodegeneration. However, the underlying biological mechanisms by which bacterial infections may lead to neurodegeneration in MS are complex and poorly understood. Here, we assessed the disease-modulating effect of an acute Escherichia coli and a chronic Staphylococcus aureus infection on the clinical course and the extent of neurodegeneration in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. In this study, we did not observe any disease modulating effect of acute E. coli infection on EAE when infection was induced in both the preclinical and in the clinical phase of the disease. However, we observed that local application of S. aureus in the preclinical phase of the disease induced a chronic systemic inflammatory response with increased in T- and B-cell counts as well as systemic production of pro-inflammatory cytokines. Unexpectedly, the infection with S. aureus completely prevented the development of clinical EAE. Moreover, it markedly decreased the extent of inflammatory infiltrates and demyelination of the optic nerve and increased the number of surviving retinal neurons. Using a S. aureus strain deficient for the extracellular adherence protein (Eap) we identified this protein to be at least partly responsible for the inhibitory effect of S. aureus infection on autoimmune inflammation of the central nervous system. Thus our results show for the first time a beneficial effect of a chronic bacterial infection on neurodegeneration in EAE and open the avenue for the design of new neuroprotective therapy in MS.
Keywords: Infection; Experimental autoimmune encephalomyelitis; Neurodegeneration
 
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