Efeito de cepas toxigênicas de Staphylococcus aureus no desenvolvimento de encefalite autoimune experimental

• Ano de defesa: 2013
• Autor(a) principal: França, Thaís Graziela Donega [UNESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Estadual Paulista (Unesp)
• Palavras-chave em Português: Encefalite; Doenças auto-imunes; Antígenos bacterianos; Camundongo como animal de laboratorio; Staphylococcus aureus; Esclerose multipla; Bacterial antigens
• Link de acesso: http://hdl.handle.net/11449/108391

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is a widely accepted model used to investigate immunopathogenic mechanisms, therapy and the effect of infectious agents on MS. In this context, this model was employed to evaluate the effect of S. aureus superantigen (SAg) producer strains on EAE development. For this C57BL/6 mice were infected with distinct S. aureus strains and three days after infection they were submitted to EAE induction by immunization with MOG (myelin oligodendrocyte glycoprotein). The effect of infections was evaluated by body weight loss, clinical score, inflammation of the CNS and cytokine production by spleen cells or CNS cells. The presence of CD4+CD25+Foxp3+ T cells (regulatory T cells) was determined in some experiments. The results were organized into 3 manuscripts. Initially, we compared the ability of 2 S. aureus strains to cause bacteremia, to migrate to the brain and their effect in the acute phase of EAE. The S. aureus strains ATCC 51650 that is a TSST-1 producer (TSST-1+) and ATCC 43300 that does not produce any SAg (TOX-) were used in this work. Both S. aureus strains were capable to cause bacteremia and migrate of the brain, however, only TOX- group caused inflammation in the brain. Both S. aureus strains were able to decrease the severity of EAE during the acute phase, but TSST-1+ strain triggered a more accentuated protective effect. Protective activity of both S. aureus strains was associated with local and peripheral cytokine modulation. In the second manuscript we investigated if the protective effect of the previous infection with S. aureus remained during the chronic disease phase. The results indicated that protection persisted during chronic EAE phase and was characterized by lower disease incidence, smaller body weight loss and also reduced clinical scores. The effect of the TSST-1+ was also more...