Velin Dominique, Favre Laurent, Bernasconi Eric, Bachmann Daniel, Pythoud Catherine, Saiji Essia, Bouzourene Hanifa, Michetti Pierre
Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
Gastroenterology. 2009 Jun;136(7):2237-2246.e1. doi: 10.1053/j.gastro.2009.02.077. Epub 2009 Mar 9.
BACKGROUND & AIMS: Despite the proven ability of immunization to reduce Helicobacter infection in mouse models, the precise mechanism of protection has remained elusive. This study explores the possibility that interleukin (IL)-17 plays a role in the reduction of Helicobacter infection following vaccination of wild-type animals or in spontaneous reduction of bacterial infection in IL-10-deficient mice.
In mice, reducing Helicobacter infection, the levels and source of IL-17 were determined and the role of IL-17 in reduction of Helicobacter infection was probed by neutralizing antibodies.
Gastric IL-17 levels were strongly increased in mice mucosally immunized with urease plus cholera toxin and challenged with Helicobacter felis as compared with controls (654 +/- 455 and 34 +/- 84 relative units for IL-17 messenger RNA expression [P < .01] and 6.9 +/- 8.4 and 0.02 +/- 0.04 pg for IL-17 protein concentration [P < .01], respectively). Flow cytometry analysis showed that a peak of CD4(+)IL-17(+) T cells infiltrating the gastric mucosa occurred in immunized mice in contrast to control mice (4.7% +/- 0.3% and 1.4% +/- 0.3% [P < .01], respectively). Gastric mucosa-infiltrating CD4(+)IL-17(+) T cells were also observed in IL-10-deficient mice that spontaneously reduced H felis infection (4.3% +/- 2.3% and 2% +/- 0.6% [P < .01], for infected and noninfected IL-10-deficient mice, respectively). In wild-type immunized mice, intraperitoneal injection of anti-IL-17 antibodies significantly inhibited inflammation and the reduction of Helicobacter infection in comparison with control antibodies (1 of 12 mice vs 9 of 12 mice reduced Helicobacter infection [P < .01], respectively).
IL-17 plays a critical role in the immunization-induced reduction of Helicobacter infection from the gastric mucosa.
尽管免疫接种在小鼠模型中已被证实有降低幽门螺杆菌感染的能力，但其确切的保护机制仍不清楚。本研究探讨白细胞介素（IL）-17在野生型动物接种疫苗后降低幽门螺杆菌感染或在IL-10缺陷小鼠细菌感染自然减少过程中发挥作用的可能性。
在小鼠中，为降低幽门螺杆菌感染，测定IL-17的水平和来源，并通过中和抗体探究IL-17在降低幽门螺杆菌感染中的作用。
与对照组相比，用脲酶加霍乱毒素进行黏膜免疫并感染猫幽门螺杆菌的小鼠胃内IL-17水平显著升高（IL-17信使核糖核酸表达的相对单位分别为654±455和34±84 [P<.01]，IL-17蛋白浓度分别为6.9±8.4和0.02±0.04 pg [P<.01]）。流式细胞术分析显示，与对照小鼠相比，免疫小鼠胃黏膜中浸润的CD4(+)IL-17(+) T细胞出现峰值（分别为4.7%±0.3%和1.4%±0.3% [P<.01]）。在自发减少猫幽门螺杆菌感染的IL-10缺陷小鼠的胃黏膜中也观察到浸润的CD4(+)IL-17(+) T细胞（感染和未感染的IL-10缺陷小鼠分别为4.3%±2.3%和2%±0.6% [P<.01]）。在野生型免疫小鼠中，与对照抗体相比，腹腔注射抗IL-17抗体显著抑制炎症反应和幽门螺杆菌感染的减少（分别有1/12只小鼠和9/12只小鼠幽门螺杆菌感染减少 [P<.01]）。
IL-17在免疫诱导的胃黏膜幽门螺杆菌感染减少中起关键作用。
