Toll-like receptor 9 processing: The key event in Toll-like receptor 9 activation?

Toll-like receptor 9 (TLR9) mediated recognition of viral and bacterial DNA activates the innate immune system. Recently proteolytic cleavage of TLR9 in the endosomal/lysosomal compartment by proteases such as cathepsins and asparagine endopeptidase (AEP) has been identified as a key step for TLR9 activation by CpG-DNA. However, mutants of TLR9 that do not affect proteolytic cleavage lost their functionality suggesting a more complex scenario of TLR9 activation.