Hirose K, Suzuki H, Nishimura H, Mitani A, Washizu J, Matsuguchi T, Yoshikai Y
Laboratory of Host Defense and Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya, Japan.
Infect Immun. 1998 Dec;66(12):5677-83. doi: 10.1128/IAI.66.12.5677-5683.1998.
Exogenous interleukin-15 (IL-15) stimulates intestinal intraepithelial lymphocytes (i-IEL) from mice to proliferate and produce gamma interferon (IFN-gamma) in vitro. To determine whether endogenous IL-15 is involved in activation of i-IEL during intestinal infection, we examined IL-15 synthesis by intestinal epithelial cells (i-EC) after infection with Listeria monocytogenes in rats. In in vitro experiments, invasion of L. monocytogenes into IEC-6 cells, a rat small intestine epithelial cell line, evidently induced IL-15 mRNA expression coincident with nuclear factor kappaB (NF-kappaB) activation, which is essential for IL-15 gene expression. IL-15 synthesis was detected in rat i-EC on day 1 after an oral inoculation of L. monocytogenes in vivo. The numbers of T-cell receptor (TCR) gamma delta+ T cells, NKR.P1(+) cells, and CD3(+) CD8(+) alpha alpha cells in i-IEL were significantly increased on day 1 after oral infection. The i-IEL from infected rats produced larger amounts of IFN-gamma upon stimulation with immobilized anti-TCR gamma delta or anti-NKR.P1 monoclonal antibodies. These results suggest that IL-15 produced by i-EC may stimulate significant fractions of i-IEL to produce IFN-gamma at an early phase of oral infection with L. monocytogenes.
外源性白细胞介素-15（IL-15）可刺激小鼠的肠道上皮内淋巴细胞（i-IEL）在体外增殖并产生γ干扰素（IFN-γ）。为了确定内源性IL-15是否参与肠道感染期间i-IEL的激活，我们检测了大鼠感染单核细胞增生李斯特菌后肠道上皮细胞（i-EC）中IL-15的合成情况。在体外实验中，单核细胞增生李斯特菌侵入大鼠小肠上皮细胞系IEC-6细胞，明显诱导了IL-15 mRNA表达，同时伴有核因子κB（NF-κB）激活，而NF-κB激活对于IL-15基因表达至关重要。在体内经口接种单核细胞增生李斯特菌后第1天，在大鼠i-EC中检测到了IL-15的合成。经口感染后第1天，i-IEL中T细胞受体（TCR）γδ+ T细胞、NKR.P1(+)细胞和CD3(+) CD8(+)αα细胞的数量显著增加。来自感染大鼠的i-IEL在用固定化抗TCRγδ或抗NKR.P1单克隆抗体刺激后产生了大量的IFN-γ。这些结果表明，i-EC产生的IL-15可能在单核细胞增生李斯特菌经口感染的早期刺激相当一部分i-IEL产生IFN-γ。
