Enhanced antibacterial potential in UBP43-deficient mice against Salmonella typhimurium infection by up-regulating type I IFN signaling

Keun Il Kim, Oxana A. Malakhova, Kasper Hoebe, Ming Yan, Bruce Beutler, Dong Er Zhang

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

ISG15 is an IFN-inducible ubiquitin-like protein and its expression and conjugation to target proteins are dramatically induced upon viral or bacterial infection. We have generated a UBP43 knockout mouse model that is lacking an ISG15-specific isopeptidase to study the biological role of the protein ISGylation system. We report that UBP43-deficient mice are hypersensitive to LPS-induced lethality and that TIR domain-containing adapter inducing IFN-β → IFN regulatory factor 3 → type I IFN is the major axis to induce protein ISGylation and UBP43 expression in macrophages upon LPS treatment. In ubp43-/- macrophages, upon LPS treatment we detected increased expression of IFN-stimulated genes, including genes for several cytokines and chemokines involved in the innate immune response. The ubp43-/- mice were able to restrict the growth of Salmonella typhimurium more efficiently than wild-type mice. These results clearly demonstrate two aspects of IFN-signaling, a beneficial effect against pathogens but a detriment to the body without strict control.

Original languageEnglish (US)
Pages (from-to)847-854
Number of pages8
JournalJournal of Immunology
Volume175
Issue number2
DOIs
StatePublished - Jul 15 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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