TOLL-LIKE RECEPTOR 4 SIGNALING LICENSES THE CYTOSOLIC TRANSPORT OF LIPOPOLYSACCHARIDE FROM BACTERIAL OUTER MEMBRANE VESICLES

作者：Gu, Lan; Meng, Ran; Tang, Yiting; Zhao, Kai; Liang, Fang; Zhang, Rui; Xue, Qianqian; Chen, Fangping; Xiao, Xianzhong; Wang, Huadong; Wang, Haichao; Billiar, Timothy R.; Lu, Ben^*

来源：Shock, 2019, 51(2): 256-265.

DOI：10.1097/SHK.0000000000001129

• Caspase-11
• noncanonical inflammation
• OMVs
• sepsis

Outer membrane vesicles (OMVs), released by variety of bacteria, are membrane-enclosed entities enriched in microbial components, toxins, and virulent factors. OMVs could deliver lipopolysaccharide (LPS) into the cytosol of host cells and subsequently activate caspase-11, which critically orchestrates immune responses and mediates septic shock. Although it is known that caspase-11 is activated by intracellular LPS, how OMVs deliver LPS into the cytosol remains largely unknown. Here we show that the activation of toll-like receptor 4 (TLR4), a LPS receptor on the cytoplasmic membrane, licenses macrophages to transport LPS from OMVs into the cytosol through TIR domain-containing adaptor-inducing interferon-b (TRIF). TRIF-mediated cytosolic delivery of LPS from OMVs depends on the production of type 1 interferon and the expression of guanylate-binding proteins (GBPs). Deletion of TRIF or GBPs prevents pyroptosis and lethality induced by OMVs or OMVs-releasing Escherichia coli. Together, these findings provide novel insight into how host coordinates extracellular and intracellular LPS sensing to orchestrate immune responses during gram-negative bacterial infection.

• 出版日期2019-2
• 单位暨南大学; 中南大学