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白细胞介素-15可能是大鼠经口感染单核细胞增生李斯特菌后肠道上皮内淋巴细胞早期活化的原因。

Interleukin-15 may be responsible for early activation of intestinal intraepithelial lymphocytes after oral infection with Listeria monocytogenes in rats.

作者信息

Hirose K, Suzuki H, Nishimura H, Mitani A, Washizu J, Matsuguchi T, Yoshikai Y

机构信息

Laboratory of Host Defense and Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya, Japan.

出版信息

Infect Immun. 1998 Dec;66(12):5677-83. doi: 10.1128/IAI.66.12.5677-5683.1998.

Abstract

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.

摘要

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。

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