Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, Australian National University, Canberra, Australia.
Cell Microbiol. 2017 Dec;19(12). doi: 10.1111/cmi.12791. Epub 2017 Oct 19.
Guanylate-binding proteins (GBPs) are a group interferon-inducible GTPases within the constellation of the dynamin GTPase superfamily. These proteins restrict the replication of intracellular pathogens in both immune and non-immune cells. GBPs and their related family members immunity-related GTPases target and lyse the membrane of the pathogen-containing vacuole, destroying the residential niche of vacuolar protozoal and bacterial pathogens. They also prevent virion infectivity and target replication complexes of ribonucleic acid viruses. The exciting concept that GBPs and immunity-related GTPases can directly target the membrane of bacteria and protozoa has emerged. Rupture and lysis of the pathogen membrane mediates liberation of concealed microbial ligands for activation of innate immune sensing pathways and the inflammasome. Further studies have demonstrated a capacity of GBPs to recruit additional antimicrobial factors, highlighting the complexity of the molecular mechanisms involved in pathogen killing. In this mini-review, we discuss recent advances describing the localisation and functions of GBPs on the host and pathogen membrane. We also highlight unresolved questions related to the regulation of GBPs in cell-autonomous immunity to intracellular pathogens.
鸟苷酸结合蛋白（GBPs）是干扰素诱导的 GTPase 家族的成员，属于动力蛋白 GTPase 超家族。这些蛋白在免疫和非免疫细胞中限制了内源性病原体的复制。GBPs 及其相关家族成员免疫相关 GTPases 靶向并裂解含有病原体的空泡的膜，破坏了空泡内原生动物和细菌病原体的居住生态位。它们还可以防止病毒粒子的感染力，并靶向 RNA 病毒的复制复合物。GBPs 和免疫相关 GTPases 可以直接靶向细菌和原生动物的膜，这一令人兴奋的概念已经出现。病原体膜的破裂和裂解介导了隐藏的微生物配体的释放，从而激活先天免疫感应途径和炎症小体。进一步的研究表明，GBPs 能够募集额外的抗菌因子，突出了参与病原体杀伤的分子机制的复杂性。在这篇迷你综述中，我们讨论了描述宿主和病原体膜上 GBPs 定位和功能的最新进展。我们还强调了与细胞自主免疫内源性病原体过程中 GBPs 调节相关的未解决问题。
