Gajendran Nadesan, Mittrücker Hans-Willi, Bordasch Karin, Heinemann Ellen, Koch Markus, Kaufmann Stefan H E
Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz 1, Berlin, 10117 Germany.
Int Immunol. 2007 Sep;19(9):1075-81. doi: 10.1093/intimm/dxm075. Epub 2007 Aug 13.
IFNgamma is critical for host defence against various food-borne pathogens including Salmonella enterica and Listeria monocytogenes, the causative agents of salmonellosis and listeriosis, respectively. We investigated the impact of regional IFNgamma expression at the intestinal epithelial barrier on host invasion by salmonellae and listeriae following oral challenge. Transgenic mice (IFNgamma-gut), generated on an IFNgamma knock-out (KO) background, selectively expressed IFNgamma in the gut driven by the modified liver fatty acid-binding protein (Fabpl(4x at -132)) promoter. Infections with attenuated S. enterica Typhimurium or with L. monocytogenes did not differ significantly in IFNgamma-KO, IFNgamma-gut and wild-type mice. Further, Listeria-specific CD4+ and CD8+ T cells were not altered in IFNgamma-gut mice. Thus, this model indicates that local IFNgamma expression by non-immunological cells in the distal part of the small intestine, caecum and colon is insufficient for prevention of gut penetration by S. enterica Typhimurium and L. monocytogenes.
干扰素γ对于宿主抵御多种食源性病原体至关重要,这些病原体包括肠炎沙门氏菌和单核细胞增生李斯特菌,它们分别是沙门氏菌病和李斯特菌病的病原体。我们研究了口服攻击后,肠道上皮屏障处局部干扰素γ表达对沙门氏菌和李斯特菌侵袭宿主的影响。在干扰素γ基因敲除(KO)背景下产生的转基因小鼠(IFNγ-肠道),在修饰的肝脏脂肪酸结合蛋白(Fabpl(4x at -132))启动子驱动下,在肠道中选择性表达干扰素γ。用减毒的鼠伤寒沙门氏菌或单核细胞增生李斯特菌感染,在干扰素γ基因敲除小鼠、IFNγ-肠道小鼠和野生型小鼠中并无显著差异。此外,IFNγ-肠道小鼠中李斯特菌特异性CD4+和CD8+ T细胞没有改变。因此,该模型表明,小肠远端、盲肠和结肠中非免疫细胞局部表达干扰素γ不足以预防鼠伤寒沙门氏菌和单核细胞增生李斯特菌穿透肠道。