干擾素刺激基因15（ISG15）是一種干擾素（IFN）-α/β-可誘導(dǎo)的,，細胞內(nèi)泛素樣蛋白。以往研究發(fā)現(xiàn),，小鼠體內(nèi)的各種蛋白質(zhì)的ISG15化（ISGylation）促進抗病毒免疫,。
本研究發(fā)現(xiàn)，某些具有ISG15遺傳性缺陷和結(jié)核分枝桿菌感染,，但不伴有病毒感染的患者,。缺乏細胞內(nèi)ISG15，沒有蛋白的ISGy化修飾與細胞對病毒的易感性無關(guān),。這與這些患者沒有罹患病毒性疾病是相一致的,。
相反，缺乏由結(jié)核分枝桿菌引起的ISG1分泌,，增加了機體對分枝桿菌病的易感性,。這是因為,，ISG1缺乏減少了包括自然殺傷細胞在內(nèi)的淋巴細胞產(chǎn)生的γ-干擾素。
這些實驗顯示,，在人類ISG化修飾對于抗病毒免疫總體來說是多余的,，但是，作為一種誘導(dǎo)γ-干擾素分泌的因子,，ISG15在最優(yōu)化抗結(jié)核免疫中起著至關(guān)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.
