TY - JOUR
T1 - Mycobacterial disease and impaired IFN-γ immunity in humans with inherited ISG15 deficiency
AU - Bogunovic, Dusan
AU - Byun, Minji
AU - Durfee, Larissa A.
AU - Abhyankar, Avinash
AU - Sanal, Ozden
AU - Mansouri, Davood
AU - Salem, Sandra
AU - Radovanovic, Irena
AU - Grant, Audrey V.
AU - Adimi, Parisa
AU - Mansouri, Nahal
AU - Okada, Satoshi
AU - Bryant, Vanessa L.
AU - Kong, Xiao Fei
AU - Kreins, Alexandra
AU - Velez, Marcela Moncada
AU - Boisson, Bertrand
AU - Khalilzadeh, Soheila
AU - Ozcelik, Ugur
AU - Darazam, Ilad Alavi
AU - Schoggins, John W.
AU - Rice, Charles M.
AU - Al-Muhsen, Saleh
AU - Behr, Marcel
AU - Vogt, Guillaume
AU - Puel, Anne
AU - Bustamante, Jacinta
AU - Gros, Philippe
AU - Huibregtse, Jon M.
AU - Abel, Laurent
AU - Boisson-Dupuis, Stéphanie
AU - Casanova, Jean Laurent
PY - 2012/9/28
Y1 - 2012/9/28
N2 - ISG15 is an interferon (IFN)-α/β-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-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.
AB - ISG15 is an interferon (IFN)-α/β-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-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.
UR - http://www.scopus.com/inward/record.url?scp=84866748115&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84866748115&partnerID=8YFLogxK
U2 - 10.1126/science.1224026
DO - 10.1126/science.1224026
M3 - Article
C2 - 22859821
AN - SCOPUS:84866748115
SN - 0036-8075
VL - 337
SP - 1684
EP - 1688
JO - Science
JF - Science
IS - 6102
ER -