Activation of alternative NF-kB signaling in the stomach: link to H. pylori virulence factors and effect on gastric inflammation and gastric pathogenesis

幽门螺杆菌（H.幽门螺杆菌）感染是世界范围内最普遍的感染之一。由细菌引起的慢性胃炎症最终可能发展为更严重的病理，最终发展为胃癌。在这一过程中，H. pylori起决定性作用。其中，经典NF-κ B通路在H.幽门螺杆菌感染已被广泛研究。相反，参与的替代，所谓的非典型，手臂的NF-κ B信号传导的胃病理学相关的H。pylori仍不清楚。我们已经有了初步的发现，表明这种替代臂参与了H。pylori诱导的炎症反应。因此，我们建议进行全面的分析，在体外以及在体内，以调查激活替代NF-κ B信号由H。通过淋巴毒素B受体（LTbR）介导幽门螺杆菌的感染，并阐明相关的分子机制，特别关注相关的细菌毒力因子。此外，通过在体内阻断或激动性激活LTbR，我们的目标是破译通过LTbR信号传导的替代性NF-κ B激活对H诱导的胃病理学的贡献。幽门感染最后，我们计划在胃中特异性表达LT，以评估其在有和无H的胃发病机制中的参与。幽门感染总之，这些实验将使我们能够建立一个因果关系之间的LT表达和LTbR介导的激活替代NF-κ B的胃发病机制，特别是在H。幽门感染

Helicobacter pylori (H. pylori) infection is one of the most prevalent infections worldwide. The chronic gastric inflammation induced by the bacterium might eventually progress to a more severe pathology and finally to gastric cancer. In this process, different host signaling pathways triggered by H. pylori play a decisive role. Of those, the role of canonical NF-kB pathway during H. pylori infection has been extensively studied. Conversely, the involvement of the alternative, so called non-canonical, arm of NF-kB signaling for gastric pathology related to H. pylori remains unclear. We have made preliminary findings indicating involvement of this alternative arm in H. pylori induced inflammatory response. Thus, we propose to perform a comprehensive analysis in vitro as well as in vivo in order to investigate the activation of alternative NF-kB signaling by H. pylori through lymphotoxin b receptor (LTbR) and to elucidate the molecular mechanisms implicated, paying special attention to bacterial virulence factors involved. In addition, by blocking or agonistically activating LTbR in vivo, we aim at deciphering the contribution of alternative NF-kB activation via LTbR-signaling to gastric pathology induced by H. pylori infection. Finally, we plan to specifically express LTs in the stomach to evaluate its involvement in gastric pathogenesis with and without H. pylori infection. Taken together, these experiments will enable us to establish a causal link between LT expression and LTbR-mediated activation of alternative NF-kB to gastric pathogenesis, particularly in the context of H. pylori infection.