干扰素刺激基因15（ISG15）是一种干扰素（IFN）-α/β-可诱导的，细胞内泛素样蛋白。以往研究发现，小鼠体内的各种蛋白质的ISG15化（ISGylation）促进抗病毒免疫。
本研究发现，某些具有ISG15遗传性缺陷和结核分枝杆菌感染，但不伴有病毒感染的患者。缺乏细胞内ISG15，没有蛋白的ISGy化修饰与细胞对病毒的易感性无关。这与这些患者没有罹患病毒性疾病是相一致的。
相反，缺乏由结核分枝杆菌引起的ISG1分泌，增加了机体对分枝杆菌病的易感性。这是因为，ISG1缺乏减少了包括自然杀伤细胞在内的淋巴细胞产生的γ-干扰素。
这些实验显示，在人类ISG化修饰对于抗病毒免疫总体来说是多余的，但是，作为一种诱导γ-干扰素分泌的因子，ISG15在最优化抗结核免疫中起着至关重要的作用。（生物谷bioon.com）
doi:10.1016/j.cell.2011.10.017
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PMID:
Mycobacterial Disease and Impaired IFN-γ Immunity in Humans with Inherited ISG15 Deficiency
Dusan Bogunovic1,Minji Byun1,Larissa A. Durfee2,*,Avinash Abhyankar1,*,Ozden Sanal3,*,Davood Mansouri4,*,Sandra Salem5,*,Irena Radovanovic5,Audrey V. Grant6,Parisa Adimi4,Nahal Mansouri1,4,Satoshi Okada1,Vanessa L. Bryant1,Xiao-Fei Kong1,Alexandra Kreins1,Marcela Moncada Velez1,Bertrand Boisson1,Soheila Khalilzadeh4,Ugur Ozcelik3,Ilad Alavi Darazam4,John W. Schoggins7,Charles M. Rice7,Saleh Al-Muhsen8,9,Marcel Behr10,Guillaume Vogt1,6,Anne Puel6,Jacinta Bustamante6,11,?,Philippe Gros5,?,Jon M. Huibregtse2,?,Laurent Abel1,6,?,Stéphanie Boisson-Dupuis1,6,Jean-Laurent Casanova1,6,12,?
ISG15 is an interferon (IFN)-α/β-inducible, ubiquitin-like intracellular protein. Its conjugation to various proteins (ISGylation) contributes to antiviral immunity in mice. We describe human patients with inherited ISG15 deficiency and mycobacterial, but not viral diseases. The lack of intracellular ISG15 production and protein ISGylation was not associated with cellular susceptibility to any viruses tested, consistent with the lack of viral diseases in these patients. By contrast, the lack of mycobacterium-induced ISG15 secretion by leukocytes—granulocytes in particular—reduced the production of IFN-γ by lymphocytes, including natural killer cells, probably accounting for the enhanced susceptibility to mycobacterial disease. This experiment of nature shows that human ISGylation is largely redundant for antiviral immunity, but that ISG15 plays an essential role as an IFN-γ–inducing secreted molecule for optimal antimycobacterial immunity.
