Abstract
BackgroundBacterial infections have been assumed to worsen multiple sclerosis (MS) disease symptoms and to lead to increased neurodegeneration. However, the underlying biological mechanisms for these effects are complex and poorly understood. Here, we assessed the disease-modulating effects of chronic infection with Staphylococcus aureus, a common human pathogen, on the clinical course and the extent of neurodegeneration in experimental autoimmune encephalomyelitis (EAE), an animal model of MS.MethodsTo conduct this study, we established a persistent chronic infection in female brown Norway rats by inoculating Staphylococcus aureus (S. aureus) bacteria in a subcutaneously implanted tissue cages.ResultsIn this study, we observed that the introduction of a localized S. aureus infection during the subclinical phase of EAE induced a chronic systemic inflammatory response, consisting of increased T- and B-cell counts and systemic production of proinflammatory cytokines. Unexpectedly, the S. aureus infection completely prevented the development of clinical EAE, and markedly reduced inflammatory infiltration and demyelination of the optic nerve, while it increased the number of surviving retinal neurons. Using a S. aureus strain that lacked the extracellular adherence protein (Eap), we determined that the extracellular adherence protein is at least partially responsible for the inhibitory effect of S. aureus infection on autoimmune inflammation of the central nervous system.ConclusionsOur results demonstrate for the first time that chronic infection with S. aureus has a beneficial effect on EAE, indicating a dual role of infection in the pathogenesis of MS. We also showed that secretion of Eap by S. aureus plays a major role in preventing autoimmune inflammation of the CNS. Moreover, we identified Eap as a factor responsible for this protective effect.
Highlights
Bacterial infections have been assumed to worsen multiple sclerosis (MS) disease symptoms and to lead to increased neurodegeneration
tissue cage fluid (TCF) obtained from infected animals contained a high number of bacteria (S. aureus), whereas no bacterial growth was observed in TCF from noninfected control animals
Using a rat model of myelin oligodendrocyte glycoprotein (MOG)-induced EAE, we have demonstrated for the first time that chronic infection with S. aureus prevents the onset of EAE and reduces the development of histopathologic changes in the optic nerve
Summary
Bacterial infections have been assumed to worsen multiple sclerosis (MS) disease symptoms and to lead to increased neurodegeneration. The underlying biological mechanisms for these effects are complex and poorly understood. We assessed the disease-modulating effects of chronic infection with Staphylococcus aureus, a common human pathogen, on the clinical course and the extent of neurodegeneration in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The underlying biological processes, especially the association of systemic infection and neurodegeneration, a major histopathological correlate of disability in MS patients, are poorly understood. Given the complexity of the interplay between infection and autoimmunity, the majority of the knowledge stems from animal studies in experimental autoimmune encephalomyelitis (EAE), an animal model of MS
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