Mycobacterial Disease And Impaired Ifn-Gamma Immunity In Humans With Inherited Isg15 Deficiency
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Tarih
2012Yazar
Bogunovic, Dusan
Byun, Minji
Durfee, Larissa A.
Abhyankar, Avinash
Sanal, Ozden
Mansouri, Davood
Salem, Sandra
Radovanovic, Irena
Grant, Audrey V.
Adimi, Parisa
Mansouri, Nahal
Okada, Satoshi
Bryant, Vanessa L.
Kong, Xiao-Fei
Kreins, Alexandra
Velez, Marcela Moncada
Boisson, Bertrand
Khalilzadeh, Soheila
Ozcelik, Ugur
Darazam, Ilad Alavi
Schoggins, John W.
Rice, Charles M.
Al-Muhsen, Saleh
Behr, Marcel
Vogt, Guillaume
Puel, Anne
Bustamante, Jacinta
Gros, Philippe
Huibregtse, Jon M.
Abel, Laurent
Boisson-Dupuis, Stephanie
Casanova, Jean-Laurent
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ISG15 is an interferon (IFN)-alpha/beta-inducible, ubiquitin-like intracellular protein. Its conjugation to various proteins (ISGylation) contributes to antiviral immunity in mice. Here, 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 that we tested, consistent with the lack of viral diseases in these patients. By contrast, the lack of mycobacterium-induced ISG15 secretion by leukocytes-granulocyte, in particular-reduced the production of IFN-gamma 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-gamma-inducing secreted molecule for optimal antimycobacterial immunity.