6533b85ffe1ef96bd12c245d

RESEARCH PRODUCT

The experimental antiphospholipid syndrome: an invaluable tool to study autoimmunity-induced neurodegeneration

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cells and its activation inhibits their differentiation and remyelination. These suggest a possible role of CNS TLR2 in progressive autoimmune demyelination. Methods: We examined the effects of intra-cerebro-ventricular (ICV) injection of Zymozan, a TLR2 agonist, on the clinical and pathological course of EAE. The survival and clinical scores were monitored; demyelination and axonal loss were quantified by gold-black and Bielschowsky stains, and the nature of neuro-inflammatory response was characterized by TLR2, IBA-1 and CD3 stainings and PCR for immune cytokines. Immune cells were isolated from EAE brain tissue and their proliferative response to the autoantigen (PLP peptide) or Concavallin A was examined in vitro. Results: Zymozan injection in naive mice induced a strong neuroinflammatory response without any clinical manifestations. In EAE mice, ICV Zymozan induced a severe acute toxic response with 80% mortality. Surviving animals returned to pre-injection clinical score, and their course of disease and CNS inflammatory parameters were not altered as compared to control EAE group. Demyelination and axonal loss were not affected by ICV Zymozan injections. Quantification of immune response in the brain by real time PCR, immunofluorescent stains and proliferative response to PLP peptide and ConA indicated an increase in innate but not adaptive immune response. Conclusions: (1) EAE mice are hypersensitive to CNS TLR2 activation with a severe toxic response. This might represent the susceptibility of multiple sclerosis patients to even trivial infections. (2) CNS TLR2 activation does not alter the clinical and pathological course of EAE. (3) These findings imply that CNS TLR2 activation affects the innate but not adaptive brain immune responses.