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 clearly 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.