期刊
JOURNAL OF IMMUNOLOGY
卷 185, 期 6, 页码 3593-3601出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1000890
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资金
- National Institutes of Health [HL091549]
- Canadian Institutes of Health Research
- Research Institute of the McGill University Health Centre
- Fonds de la Recherche en Sante du Quebec
To deepen our knowledge of the natural host response to pathogens, our team undertook an in vivo screen of mutagenized 129S1 mice with Salmonella Typhimurium. One mutation affecting Salmonella susceptibility was mapped to a region of 1.3 Mb on chromosome 6 that contains 15 protein-coding genes. A missense mutation was identified in the Usp18 (ubiquitin-specific peptidase 18) gene. This mutation results in an increased inflammatory response (IL-6, type 1 IFN) to Salmonella and LPS challenge while paradoxically reducing IFN-gamma production during bacterial infection. Increased STAT1 phosphorylation correlated with impaired STAT4 phosphorylation, resulting in overwhelming IL-6 secretion but reduced IFN-gamma production during infection. The reduced IFN-gamma levels, along with the increased inflammation, rationalize the S. Typhimurium susceptibility in terms of increased bacterial load in target organs and cytokine-induced septic shock and death. The Journal of Immunology, 2010, 185: 3593-3601.
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