Publication Date:
2012-08-04
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507439/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507439/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- 1R37AI095983-01/AI/NIAID NIH HHS/ -- 5R01AI035237-15/AI/NIAID NIH HHS/ -- 8UL1TR000043/TR/NCATS NIH HHS/ -- AI096090/AI/NIAID NIH HHS/ -- CA072943/CA/NCI NIH HHS/ -- R01 AI035237/AI/NIAID NIH HHS/ -- R01 AI091707/AI/NIAID NIH HHS/ -- R01 AI096090/AI/NIAID NIH HHS/ -- R01 CA072943/CA/NCI NIH HHS/ -- R37 AI095983/AI/NIAID NIH HHS/ -- UL1 TR000043/TR/NCATS NIH HHS/ -- New York, N.Y. -- Science. 2012 Sep 28;337(6102):1684-8. Epub 2012 Aug 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22859821" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antibodies, Viral/blood
;
Cytokines/genetics/*immunology
;
Female
;
Granulocytes/immunology
;
Humans
;
Immunity
;
Interferon-gamma/*immunology
;
Interleukin-12/immunology
;
Killer Cells, Natural/immunology
;
Male
;
Mice
;
Mycobacterium Infections/blood/genetics/*immunology
;
Pedigree
;
T-Lymphocytes/immunology
;
Ubiquitins/genetics/*immunology
;
Virus Diseases/blood/*immunology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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