香港中文大学于君等研究人员合作发现，咽峡炎链球菌促进小鼠胃部炎症、萎缩和肿瘤发生。2024年1月30日，《细胞》杂志在线发表了这项成果。
研究人员发现，咽峡炎链球菌（S. anginosus）在小鼠胃中定植并诱发急性胃炎。在常规小鼠中，S. anginosus感染可自发诱发进行性慢性胃炎、壁细胞萎缩、粘液变性和发育不良，这些结果在无菌小鼠中得到了证实。此外，在致癌物质诱导的胃肿瘤发生和YTN16胃癌（GC）细胞同种移植中，S. anginosus会加速GC的发展。一致的是，S. anginosus破坏胃屏障功能、促进细胞增殖并抑制细胞凋亡。
从机理上讲，研究人员发现了一种S. anginosus表面蛋白TMPC，它能与胃上皮细胞上的Annexin A2（ANXA2）受体相互作用。TMPC与ANXA2的相互作用介导了S. anginosus的附着和定植，并诱导了丝裂原活化蛋白激酶（MAPK）的激活。ANXA2基因敲除可抑制S. anginosus对MAPK的诱导。因此，这项研究揭示了S. anginosus是一种通过与胃上皮细胞，在TMPC-ANXA2-MAPK轴上的直接相互作用促进胃肿瘤发生的病原体。
据悉，在GC患者的胃粘膜中富集了S. anginosus。
附：英文原文
Title: Streptococcus anginosus promotes gastric inflammation, atrophy, and tumorigenesis in mice
Author: Kaili Fu, Alvin Ho Kwan Cheung, Chi Chun Wong, Weixin Liu, Yunfei Zhou, Feixue Wang, Pingmei Huang, Kai Yuan, Olabisi Oluwabukola Coker, Yasi Pan, Danyu Chen, Nga Man Lam, Mengxue Gao, Xiang Zhang, He Huang, Ka Fai To, Joseph Jao Yiu Sung, Jun Yu
Issue&Volume: 2024-01-30
Abstract: Streptococcus anginosus (S. anginosus) was enriched in the gastric mucosa of patients with gastric cancer (GC). Here, we show that S. anginosus colonized the mouse stomach and induced acute gastritis. S. anginosus infection spontaneously induced progressive chronic gastritis, parietal cell atrophy, mucinous metaplasia, and dysplasia in conventional mice, and the findings were confirmed in germ-free mice. In addition, S. anginosus accelerated GC progression in carcinogen-induced gastric tumorigenesis and YTN16 GC cell allografts. Consistently, S. anginosus disrupted gastric barrier function, promoted cell proliferation, and inhibited apoptosis. Mechanistically, we identified an S. anginosus surface protein, TMPC, that interacts with Annexin A2 (ANXA2) receptor on gastric epithelial cells. Interaction of TMPC with ANXA2 mediated attachment and colonization of S. anginosus and induced mitogen-activated protein kinase (MAPK) activation. ANXA2 knockout abrogated the induction of MAPK by S. anginosus. Thus, this study reveals S. anginosus as a pathogen that promotes gastric tumorigenesis via direct interactions with gastric epithelial cells in the TMPC-ANXA2-MAPK axis.
DOI: 10.1016/j.cell.2024.01.004
Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00006-0