Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, 27710, USA.
Department of Immunology, Duke University Medical Center, Durham, NC, 27710, USA.
Cell Microbiol. 2017 Dec;19(12). doi: 10.1111/cmi.12793. Epub 2017 Oct 17.
Most bacterial pathogens enter and exit eukaryotic cells during their journey through the vertebrate host. In order to endure inside a eukaryotic cell, bacterial invaders commonly employ bacterial secretion systems to inject host cells with virulence factors that co-opt the host's membrane trafficking systems and thereby establish specialised pathogen-containing vacuoles (PVs) as intracellular niches permissive for microbial growth and survival. To defend against these microbial adversaries hiding inside PVs, host organisms including humans evolved an elaborate cell-intrinsic armoury of antimicrobial weapons that include noxious gases, antimicrobial peptides, degradative enzymes, and pore-forming proteins. This impressive defence machinery needs to be accurately delivered to PVs, in order to fight off vacuole-dwelling pathogens. Here, I discuss recent evidence that the presence of bacterial secretion systems at PVs and the associated destabilisation of PV membranes attract such antimicrobial delivery systems consisting of sugar-binding galectins as well as dynamin-like guanylate-binding proteins (GBPs). I will review recent advances in our understanding of intracellular immune recognition of PVs by galectins and GBPs, discuss how galectins and GBPs control host defence, and highlight important avenues of future research in this exciting area of cell-autonomous immunity.
大多数细菌病原体在通过脊椎动物宿主的过程中进入和离开真核细胞。为了在真核细胞内存活，细菌入侵物通常利用细菌分泌系统将毒力因子注入宿主细胞，这些毒力因子会劫持宿主的膜运输系统，从而建立专门的含有病原体的空泡（PV）作为允许微生物生长和存活的细胞内小生境。为了抵御隐藏在 PV 中的这些微生物敌人，包括人类在内的宿主生物进化出了一套精细的细胞内抗菌武器库，其中包括有害气体、抗菌肽、降解酶和形成孔的蛋白质。为了击退在空泡中生存的病原体，这种令人印象深刻的防御机制需要准确地输送到 PV 中。在这里，我将讨论最近的证据，即 PV 上存在细菌分泌系统以及相关的 PV 膜不稳定会吸引包括糖结合半乳糖凝集素和类似 dynamin 的鸟苷酸结合蛋白（GBP）在内的这种抗菌输送系统。我将回顾我们对半乳糖凝集素和 GBP 对内质网免疫识别的理解的最新进展，讨论半乳糖凝集素和 GBP 如何控制宿主防御，并强调该令人兴奋的细胞自主免疫领域未来研究的重要途径。
