Innate immunity mediated by TLR9 modulates pathogenicity in an animal model of multiple sclerosis

2006 | journal article. A publication with affiliation to the University of Göttingen.

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​Innate immunity mediated by TLR9 modulates pathogenicity in an animal model of multiple sclerosis​
Prinz, M. R.; Garbe, F.; Schmidt, H.; Mildner, A.; Gutcher, I.; Wolter, K. & Piesche, M. et al.​ (2006) 
Journal of Clinical Investigation116(2) pp. 456​-464​.​ DOI: https://doi.org/10.1172/JCI26078 

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Authors
Prinz, Marco R.; Garbe, F.; Schmidt, H.; Mildner, Alexander; Gutcher, Ilona; Wolter, Karina; Piesche, Matthias; Schroers, Roland; Weiss, Elisabeth; Kirschning, C. J.; Rochford, CDP; Bruck, Wolfgang W.; Becher, Burkhard
Abstract
Inflammatory diseases of the CNS, such as MS and its animal model EAE, are characterized by infiltration of activated lymphocytes and phagocytes into the CNS. Within the CNS, activation of resident cells initiates an inflammatory cascade, leading to tissue destruction, demyelination, and neurologic deficit. TLRs recognize microbes and are pivotal mediators of innate immunity. Within the CNS, augmented TLR expression during EAE is observed, even in the absence of any apparent microbial involvement. To determine the functional relevance of this phenomenon during sterile autoimmunity, we studied the role of different TLRs as well as their common signaling adaptor MyD88 in the development of EAE. We found that MyD88(-/-) mice were completely EAE resistant. Surprisingly, this protection is partly due to engagement of the CpG receptor TLR9. Restricting the MyD88 or TLR9 mutation to host radio-resistant cells. including the cells within the CNS, revealed that engagement of radio-resistant cells modulated the disease course and histopathological changes. Our data dearly demonstrate that both TLR9 and MyD88 are essential modulators of the autoimmune process during the effector phase of disease and suggest that endogenous "danger signals" modulate the disease pathogenesis.
Issue Date
2006
Status
published
Publisher
Amer Soc Clinical Investigation Inc
Journal
Journal of Clinical Investigation 
ISSN
0021-9738

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