Calpain-2 facilitates infection of the intracellular bacteria Listeria monocytogenes and invasion intestinal immune barrier by impairing nitric oxide homeostasis

作者：Bo Yao, Jingru Wang, Dingyu Hou, Weiming Liu, Chenke Xie, Kai Shi, Wenyi Han, Xiaofeng Miao, Jun Chen, Zhihui Cai, Hui Yang, Qinjie Ling, Kai Yin, Zhongjun Dong, Zhi Huang · 发表于：Journal of Advanced Research · 年份：2025 · DOI：10.1016/j.jare.2025.08.043 · 被引用次数：2 · 研究领域：Calpain Protease Function and Regulation、Meat and Animal Product Quality、Cardiovascular, Neuropeptides, and Oxidative Stress Research

INTRODUCTION: The ubiquitously expressed enzymes, calpain-1 and -2 (CAPN1 and 2) play important roles in a wide variety of physiological and pathological processes including infection and immune responses. CAPN2 is of particular interest due to its role in regulating intracellular bacterial infection and invasion, but the underlying mechanisms remain to be elucidated. OBJECTIVES: In this study, we focused on intestinal CAPN2 involved in infection by the intracellular bacteria Listeria monocytogenes (L. monocytogenes) which invade the intestinal immune barrier Peyer's patches by impairing nitric oxide (NO) homeostasis. METHODS: L. monocytogenes infection by intragastric inoculation and intestinal ligated loops was performed in mice with deletion of the endogenous calpain inhibitory protein, calpastatin (CAST), or the use of a CAPN2 specific inhibitor (CAPN2-Inh). The invasion of L. monocytogenes, the activation of CAPN2, and their dependence on NO were investigated using inducible nitric oxide synthase (iNOS) knockout mice. The effects of CAPN mediated decrease in NO production and the subsequent modulation of L. monocytogenes infection and cell-to-cell transmission were confirmed in macrophages using flow cytometry and fluorescence tracing. RESULTS: Database analysis indicated dynamic CAPN2 activation and expression during L. monocytogenes infection, which was confirmed in our infection models as well as macrophage experiments. CAPN2 was found to regulate iNOS mediated NO pro...