title: Mycobacterial disease and impaired IFN-γ immunity in humans with inherited ISG15 deficiency.
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.
authors.affiliation: St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
authors.forename: Dusan
authors.initials: D
authors.lastname: Bogunovic
authors.forename: Minji
authors.initials: M
authors.lastname: Byun
authors.forename: Larissa A
authors.initials: LA
authors.lastname: Durfee
authors.forename: Avinash
authors.initials: A
authors.lastname: Abhyankar
authors.forename: Ozden
authors.initials: O
authors.lastname: Sanal
authors.forename: Davood
authors.initials: D
authors.lastname: Mansouri
authors.forename: Sandra
authors.initials: S
authors.lastname: Salem
authors.forename: Irena
authors.initials: I
authors.lastname: Radovanovic
authors.forename: Audrey V
authors.initials: AV
authors.lastname: Grant
authors.forename: Parisa
authors.initials: P
authors.lastname: Adimi
authors.forename: Nahal
authors.initials: N
authors.lastname: Mansouri
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okada
authors.forename: Vanessa L
authors.initials: VL
authors.lastname: Bryant
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Kong
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kreins
authors.forename: Marcela Moncada
authors.initials: MM
authors.lastname: Velez
authors.forename: Bertrand
authors.initials: B
authors.lastname: Boisson
authors.forename: Soheila
authors.initials: S
authors.lastname: Khalilzadeh
authors.forename: Ugur
authors.initials: U
authors.lastname: Ozcelik
authors.forename: Ilad Alavi
authors.initials: IA
authors.lastname: Darazam
authors.forename: John W
authors.initials: JW
authors.lastname: Schoggins
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rice
authors.forename: Saleh
authors.initials: S
authors.lastname: Al-Muhsen
authors.forename: Marcel
authors.initials: M
authors.lastname: Behr
authors.forename: Guillaume
authors.initials: G
authors.lastname: Vogt
authors.forename: Anne
authors.initials: A
authors.lastname: Puel
authors.forename: Jacinta
authors.initials: J
authors.lastname: Bustamante
authors.forename: Philippe
authors.initials: P
authors.lastname: Gros
authors.forename: Jon M
authors.initials: JM
authors.lastname: Huibregtse
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Boisson-Dupuis
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D005260:Female; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D007109:Immunity; D007371:Interferon-gamma / Q000276:immunology*; D018664:Interleukin-12 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D051379:Mice; D009164:Mycobacterium Infections / Q000097:blood / Q000235:genetics / Q000276:immunology*; D010375:Pedigree; D013601:T-Lymphocytes / Q000276:immunology; D014452:Ubiquitins / Q000235:genetics / Q000276:immunology*; D014777:Virus Diseases / Q000097:blood / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D014452:Ubiquitins; D018664:Interleukin-12; C074034:ISG15 protein, human; D007371:Interferon-gamma