Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection

• 岩井, 一宏

  Department of Molecular and Cellular Physiology, Graduate School of Medicine, Kyoto University,

• Reese, Tiffany A.

• Kimmey, Jacqueline M.

• Weiss, Leslie A.

• Song, Christina

• Zhang, Xin

• Kambal, Amal

• Duan, Erning

• Carrero, Javier A.

• Boisson, Bertrand

• Laplantine, Emmanuel

• Israel, Alain

• Picard, Capucine

• Colonna, Marco

• Edelson, Brian T.

• Sibley, L. David

• Stallings, Christina L.

• Casanova, Jean Laurent

• Iwai, Kazuhiro

• Virgin, Herbert W.

抄録

Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exhibit amylopectin-like deposits in the myocardium but show minimal signs of hyper-inflammation. However, they show immunodeficiency upon acute infection with Listeria monocytogenes, Toxoplasma gondii or Citrobacter rodentium. Increased susceptibility to Listeria was due to HOIL-1 function in hematopoietic cells and macrophages in production of protective cytokines. In contrast, HOIL-1-deficient mice showed enhanced control of chronic Mycobacterium tuberculosis or murine γ-herpesvirus 68 (MHV68), and these infections conferred a hyper-inflammatory phenotype. Surprisingly, chronic infection with MHV68 complemented the immunodeficiency of HOIL-1, IL-6, Caspase-1 and Caspase-1;Caspase-11-deficient mice following Listeria infection. Thus chronic herpesvirus infection generates signs of auto-inflammation and complements genetic immunodeficiency in mutant mice, highlighting the importance of accounting for the virome in genotype-phenotype studies.

収録刊行物

• eLife

  eLife 4 2015-01-20

  eLife Sciences Publications Ltd

詳細情報

• CRID: 1050564285794567936
• NII論文ID: 120005997705
• ISSN: 2050084X
• HANDLE: 2433/218636
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles