An essential role for the N-terminal fragmentof Toll-like receptor 9 in DNA sensing

摘要

Toll-like receptor 9 (TLR9) is an innate immune sensor for microbial DNA that erroneouslyresponds to self DNA in autoimmune disease. To prevent autoimmune responses, Toll-likereceptor 9 is excluded from the cell surface and silenced until the N-terminal half of theectodomain (TLR9N) is cleaved off in the endolysosome. Truncated Toll-like receptor 9(TLR9C) senses ingested microbial DNA, although the precise role of the truncation remainscontroversial. Here we show that TLR9 is expressed on the surface of splenic dendritic cells.Following the cleavage of TLR9 in the endolysosome, N-terminal half of the ectodomainremains associated with truncated TLR9, forming the complex TLR9NtC. The TLR9-dependent cytokine production by Tlr9/ dendritic cells is rescued by a combination ofTLR9N and TLR9C, but not by TLR9C alone. These results demonstrate that the TLR9NtCcomplex is a bona fide DNA sensor.