Mycobacterial disease and impaired IFN-γ immunity in humans with inherited ISG15 deficiency

Dusan Bogunovic, Minji Byun, Larissa A. Durfee, Avinash Abhyankar, Ozden Sanal, Davood Mansouri, Sandra Salem, Irena Radovanovic, Audrey V. Grant, Parisa Adimi, Nahal Mansouri, Satoshi Okada, Vanessa L. Bryant, Xiao Fei Kong, Alexandra Kreins, Marcela Moncada Velez, Bertrand Boisson, Soheila Khalilzadeh, Ugur Ozcelik, Ilad Alavi DarazamJohn W. Schoggins, Charles M. Rice, Saleh Al-Muhsen, Marcel Behr, Guillaume Vogt, Anne Puel, Jacinta Bustamante, Philippe Gros, Jon M. Huibregtse, Laurent Abel, Stéphanie Boisson-Dupuis, Jean Laurent Casanova

Research output: Contribution to journalArticle

231 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1684-1688
Number of pages5
JournalScience
Volume337
Issue number6102
DOIs
StatePublished - Sep 28 2012

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Interferons
Immunity
Virus Diseases
Antiviral Agents
Ubiquitins
Mycobacterium
Granulocytes
Natural Killer Cells
Proteins
Leukocytes
Lymphocytes
Viruses

ASJC Scopus subject areas

  • General

Cite this

Bogunovic, D., Byun, M., Durfee, L. A., Abhyankar, A., Sanal, O., Mansouri, D., ... Casanova, J. L. (2012). Mycobacterial disease and impaired IFN-γ immunity in humans with inherited ISG15 deficiency. Science, 337(6102), 1684-1688. https://doi.org/10.1126/science.1224026

Mycobacterial disease and impaired IFN-γ immunity in humans with inherited ISG15 deficiency. / 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, Stéphanie; Casanova, Jean Laurent.

In: Science, Vol. 337, No. 6102, 28.09.2012, p. 1684-1688.

Research output: Contribution to journalArticle

Bogunovic, D, Byun, M, Durfee, LA, Abhyankar, A, Sanal, O, Mansouri, D, Salem, S, Radovanovic, I, Grant, AV, Adimi, P, Mansouri, N, Okada, S, Bryant, VL, Kong, XF, Kreins, A, Velez, MM, Boisson, B, Khalilzadeh, S, Ozcelik, U, Darazam, IA, Schoggins, JW, Rice, CM, Al-Muhsen, S, Behr, M, Vogt, G, Puel, A, Bustamante, J, Gros, P, Huibregtse, JM, Abel, L, Boisson-Dupuis, S & Casanova, JL 2012, 'Mycobacterial disease and impaired IFN-γ immunity in humans with inherited ISG15 deficiency', Science, vol. 337, no. 6102, pp. 1684-1688. https://doi.org/10.1126/science.1224026
Bogunovic D, Byun M, Durfee LA, Abhyankar A, Sanal O, Mansouri D et al. Mycobacterial disease and impaired IFN-γ immunity in humans with inherited ISG15 deficiency. Science. 2012 Sep 28;337(6102):1684-1688. https://doi.org/10.1126/science.1224026
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, Stéphanie ; Casanova, Jean Laurent. / Mycobacterial disease and impaired IFN-γ immunity in humans with inherited ISG15 deficiency. In: Science. 2012 ; Vol. 337, No. 6102. pp. 1684-1688.
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