Data from: Defining the roles of IFN-gamma and IL-17A in inflammation and protection against Helicobacter pylori infection

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CD4+ T cells have been shown to be essential for vaccine-induced protection against Helicobacter pylori infection. However, the effector mechanisms leading to reductions in the gastric bacterial loads of vaccinated mice remain unclear. We have investigated the function of IFN-γ and IL-17A for vaccine-induced protection and inflammation (gastritis) using IFN-γ-gene-knockout (IFN-γ-/-) mice, after sublingual or intragastric immunization with H. pylori lysate antigens and cholera toxin. Bacteria were enumerated in the stomachs of mice and related to the gastritis score and cellular immune responses. We report that sublingually and intragastrically immunized IFN-γ-/- mice had significantly reduced bacterial loads similar to immunized wild-type mice compared to respective unimmunized infection controls. The reduction in bacterial loads in sublingually and intragastrically immunized IFN-γ-/- mice was associated with significantly higher levels of IL-17A in stomach extracts and lower gastritis scores compared with immunized wild-type mice. To study the role of IL-17A for vaccine-induced protection in sublingually immunized IFN-γ-/- mice, IL-17A was neutralized in vivo at the time of infection. Remarkably, the neutralization of IL-17A in sublingually immunized IFN-γ-/- mice completely abolished protection against H. pylori infection and the mild gastritis. In summary, our results suggest that IFN-γ responses in the stomach of sublingually immunized mice promote vaccine-induced gastritis, after infection with H. pylori but that IL-17A primarily functions to reduce the bacterial load.

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已有研究表明，CD4阳性T细胞（CD4+ T cells）对于疫苗诱导的抗幽门螺杆菌（Helicobacter pylori）感染保护作用至关重要。然而，导致疫苗接种小鼠胃内细菌载量降低的效应机制仍不明确。本研究采用干扰素γ基因敲除（IFN-γ-gene-knockout, IFN-γ⁻/⁻）小鼠，以幽门螺杆菌裂解物抗原联合霍乱毒素（cholera toxin）经舌下或胃内途径免疫，探究了干扰素γ（IFN-γ）与白细胞介素17A（IL-17A）在疫苗诱导保护及炎症（胃炎）中的作用。研究人员对小鼠胃部的细菌载量进行了定量检测，并将其与胃炎评分及细胞免疫应答进行关联分析。

结果显示，与对应的未免疫感染对照组相比，经舌下或胃内免疫的干扰素γ基因敲除小鼠的细菌载量显著降低，且该降幅与免疫后的野生型小鼠相当。相较于免疫后的野生型小鼠，经舌下或胃内免疫的干扰素γ基因敲除小鼠的胃组织提取物中白细胞介素17A水平显著升高，同时胃炎评分更低，这与其细菌载量降低呈显著相关。

为探究白细胞介素17A（IL-17A）在舌下免疫的干扰素γ基因敲除小鼠疫苗诱导保护中的作用，本研究于感染同时对小鼠体内的白细胞介素17A进行了中和处理。值得注意的是，在舌下免疫的干扰素γ基因敲除小鼠体内中和白细胞介素17A后，其抗幽门螺杆菌感染的保护作用及伴随的轻度胃炎均被完全消除。

综上，本研究结果表明：幽门螺杆菌感染后，舌下免疫小鼠胃部的干扰素γ（IFN-γ）应答会促进疫苗诱导的胃炎；而白细胞介素17A（IL-17A）则主要发挥降低细菌载量的功能。