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

Toll-like receptor 9 (TLR9) is an innate immune sensor for microbial DNA that erroneously responds to self DNA in autoimmune disease. To prevent autoimmune responses, Toll-like receptor 9 is excluded from the cell surface and silenced until the N-terminal half of the ectodomain (TLR9N) is cleaved off in the endolysosome. Truncated Toll-like receptor 9 (TLR9C) senses ingested microbial DNA, although the precise role of the truncation remains controversial. 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 ectodomain remains associated with truncated TLR9, forming the complex TLR9N + C. The TLR9-dependent cytokine production by Tlr9(-/-) dendritic cells is rescued by a combination of TLR9N and TLR9C, but not by TLR9C alone. These results demonstrate that the TLR9N + C complex is a bona fide DNA sensor

Enhancement of an anti-tumor immune response by transient blockade of central T cell tolerance

Thymic central tolerance is a critical process that prevents autoimmunity but also presents a challenge to the generation of anti-tumor immune responses. Medullary thymic epithelial cells (mTECs) eliminate self-reactive T cells by displaying a diverse rep

NAIP/NLRC4 inflammasome activation in MRP8+ cells is sufficient to cause systemic inflammatory disease

Inflammasomes are protein complexes induced by pathogens for the secretion of pro-inflammatory cytokines IL-1β and IL-18 in immune cells. Here the authors show, using a new mouse model, that aberrant NLRC4 and ASC-dependent inflammasome activation in neutrophils contributes to systemic inflammation