Norwegian University of Science and Technology, Department of Cancer Research and Molecular Medicine, N-7489 Trondheim, Norway.
Immunity. 2010 Oct 29;33(4):583-96. doi: 10.1016/j.immuni.2010.09.010. Epub 2010 Oct 7.
Toll-like receptor 4 (TLR4) is indispensable for recognition of Gram-negative bacteria. We described a trafficking pathway for TLR4 from the endocytic recycling compartment (ERC) to E. coli phagosomes. We found a prominent colocalization between TLR4 and the small GTPase Rab11a in the ERC, and Rab11a was involved in the recruitment of TLR4 to phagosomes in a process requiring TLR4 signaling. Also, Toll-receptor-associated molecule (TRAM) and interferon regulatory factor-3 (IRF3) localized to E. coli phagosomes and internalization of E. coli was required for a robust interferon-β induction. Suppression of Rab11a reduced TLR4 in the ERC and on phagosomes leading to inhibition of the IRF3 signaling pathway induced by E. coli, whereas activation of the transcription factor NF-κB was unaffected. Moreover, Rab11a silencing reduced the amount of TRAM on phagosomes. Thus, Rab11a is an important regulator of TLR4 and TRAM transport to E. coli phagosomes thereby controlling IRF3 activation from this compartment.
Toll 样受体 4（TLR4）对于识别革兰氏阴性细菌是不可或缺的。我们描述了 TLR4 从内体再循环区（ERC）到大肠杆菌吞噬体的运输途径。我们发现 TLR4 在 ERC 中与小 GTP 酶 Rab11a 之间有明显的共定位，Rab11a 参与了 TLR4 在需要 TLR4 信号的过程中向吞噬体的募集。此外，Toll 受体相关分子（TRAM）和干扰素调节因子-3（IRF3）定位于大肠杆菌吞噬体，并且大肠杆菌的内化对于干扰素-β的强烈诱导是必需的。Rab11a 的抑制减少了 ERC 中的 TLR4 和吞噬体上的 TLR4，从而抑制了由大肠杆菌诱导的 IRF3 信号通路，而转录因子 NF-κB 的激活不受影响。此外，Rab11a 沉默减少了吞噬体上的 TRAM 数量。因此，Rab11a 是 TLR4 和 TRAM 向大肠杆菌吞噬体运输的重要调节剂，从而控制该区域的 IRF3 激活。
