Vaccination of mice against H pylori induces a strong Th-17 response and immunity that is neutrophil dependent.
Vaccination of mice against H pylori induces a strong Th-17 response and immunity that is neutrophil dependent.
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DOI：
10.1053/j.gastro.2008.09.017
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发表时间：
2009-01
期刊：
影响因子：
29.4
通讯作者：
Blanchard TG
中科院分区：
文献类型：
--
作者：
DeLyria ES;Redline RW;Blanchard TG
针对胃幽门螺杆菌感染的疫苗效力已在小鼠中得到证实，但对细菌清除的效应机制知之甚少。我们的目的是研究疫苗诱导保护的可能的T细胞-中性粒细胞途径。比较未免疫和免疫小鼠对H.幽门螺杆菌攻毒。通过回忆测定评估T细胞应答。IL-17诱导的白细胞和非白细胞细胞的趋化因子的生产进行了评价细胞因子ELISA。在动力学研究中，在激发后的多个时间点收集活检组织，并评估细菌负荷和炎症。通过定量PCR测定T细胞、IL-17、IFNγ、MIP-2、KC和LIX的相对水平。通过攻毒后抗体介导的中性粒细胞耗竭评价中性粒细胞的作用。免疫诱导强烈的产生IFNγ和IL-17的T细胞应答，并且IL-17能够从树突状细胞、巨噬细胞、成纤维细胞和胃上皮细胞诱导显著量的KC和MIP-2。免疫小鼠的攻击诱导的胃炎显著大于感染小鼠，在第7天之前显著降低细菌负荷。在免疫小鼠中，T细胞向胃粘膜的募集与IL-17和IFNγ的持续升高相关，随后是KC、MIP-2和LIX的产生以及第5天大量中性粒细胞的募集。抗体介导的中性粒细胞耗竭废除疫苗效力。小鼠H.幽门螺杆菌导致显著的Th-17细胞回忆应答，该应答与趋化因子的增加有关，趋化因子将中性粒细胞吸引到胃中，这对于根除幽门螺杆菌是重要的。幽门。
Vaccine efficacy against gastric Helicobacter pylori infection has been demonstrated in mice, but little is known about the effector mechanisms of bacterial clearance. Our aim was to investigate a possible T cell-neutrophil pathway of vaccine-induced protection. Nonimmune and immunized mice were compared for their response to H. pylori challenge. T cell responses were assessed by recall assays. IL-17-induced chemokine production by leukocyte and nonleukocyte cells was evaluated by cytokine ELISA. In a kinetic study, biopsies were collected at multiple time points post-challenge and assessed for bacterial load and inflammation. Relative levels of T cells, IL-17, IFNγ, MIP-2, KC, and LIX were determined by quantitative PCR. The role of neutrophils was evaluated by antibody-mediated depletion of neutrophils following challenge. Immunization induced strong IFNγ and IL-17-producing T cell responses, and IL-17 was capable of inducing significant amounts of KC and MIP-2 from dendritic cells, macrophages, fibroblasts, and gastric epithelial cells. Challenge of immunized mice induced significantly greater gastritis than infected mice, preceding significantly lower bacterial loads by day 7. In immune mice, T cell recruitment to the gastric mucosa correlated with a continuous rise in IL-17 and IFNγ, followed by KC, MIP-2, and LIX production and the recruitment of significant numbers of neutrophils by day 5. Antibody-mediated depletion of neutrophils abrogated vaccine efficacy. Vaccination of mice against H. pylori results in a significant Th-17 cell recall response associated with increases in chemokines that attract neutrophils to the stomach which are important for eradication of H. pylori.