title: Beneficial effect of chronic Staphylococcus aureus infection in a model of multiple sclerosis is mediated through the secretion of extracellular adherence protein.
abstract: BACKGROUND
  Bacterial 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.
  
  
  METHODS
  To 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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  Our 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.
authors: Department of Neurology, University Medicine Goettingen, Robert-Koch-Strasse 40, 37075, Goettingen, Germany. singh_prats31@yahoo.co.in.
authors: Prateek
authors: P
authors: Kumar
authors: Department of Neurology, University Medicine Goettingen, Robert-Koch-Strasse 40, 37075, Goettingen, Germany. Benedikt.Kretzschmar@medizin.uni-goettingen.de.
authors: Benedikt
authors: B
authors: Kretzschmar
authors: Department of Neurology, University Medicine Goettingen, Robert-Koch-Strasse 40, 37075, Goettingen, Germany. sabine.herold@med.uni-goettingen.de.
authors: Sabine
authors: S
authors: Herold
authors: Institute of Neuropathology, University Medicine Goettingen, Goettingen, 37075, Germany. rnau@gwdg.de.
authors: Roland
authors: R
authors: Nau
authors: Department of Pathology and Immunology, Centre Médical Universitaire 1, Rue Michel-Servet 1211, Geneva 4, Switzerland. mario.kreutzfeldt@googlemail.com.
authors: Mario
authors: M
authors: Kreutzfeldt
authors: Institute of Neuropathology, University Medicine Goettingen, Goettingen, 37075, Germany. Sebert1@gwdg.de.
authors: Sandra
authors: S
authors: Schütze
authors: Department of Neurology, University Medicine Goettingen, Robert-Koch-Strasse 40, 37075, Goettingen, Germany. mbaehr@gwdg.de.
authors: Mathias
authors: M
authors: Bähr
authors: Department of Neurology, University Medicine Goettingen, Robert-Koch-Strasse 40, 37075, Goettingen, Germany. k.hein@uni-goettingen.de.
authors: Katharina
authors: K
authors: Hein
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology; D001426:Bacterial Proteins / Q000378:metabolism*; D002452:Cell Count; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000209:etiology; D007962:Leukocytes / Q000473:pathology; D009103:Multiple Sclerosis / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D009900:Optic Nerve / Q000473:pathology; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D012160:Retina / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000473:pathology; D013203:Staphylococcal Infections / Q000150:complications*; D013211:Staphylococcus aureus / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; C444739:Eap-N protein, Staphylococcus aureus; D063308:Myelin-Oligodendrocyte Glycoprotein; D016601:RNA-Binding Proteins
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