CSIR-Centre for Cellular and Molecular Biology, Hyderabad, Telangana, India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
Helicobacter. 2024 Mar-Apr;29(2):e13069. doi: 10.1111/hel.13069.
Helicobacter pylori (H. pylori) seems to play causative roles in gastric cancers. H. pylori has also been detected in established gastric cancers. How the presence of H. pylori modulates immune response to the cancer is unclear. The cytotoxicity of natural killer (NK) cells, toward infected or malignant cells, is controlled by the repertoire of activating and inhibitory receptors expressed on their surface. Here, we studied H. pylori-induced changes in the expression of ligands, of activating and inhibitory receptors of NK cells, in the gastric adenocarcinoma AGS cells, and their impacts on NK cell responses. AGS cells lacked or had low surface expression of the class I major histocompatibility complex (MHC-I) molecules HLA-E and HLA-C-ligands of the major NK cell inhibitory receptors NKG2A and killer-cell Ig-like receptor (KIR), respectively. However, AGS cells had high surface expression of ligands of activating receptors DNAM-1 and CD2, and of the adhesion molecules LFA-1. Consistently, AGS cells were sensitive to killing by NK cells despite the expression of inhibitory KIR on NK cells. Furthermore, H. pylori enhanced HLA-C surface expression on AGS cells. H. pylori infection enhanced HLA-C protein synthesis, which could explain H. pylori-induced HLA-C surface expression. H. pylori infection enhanced HLA-C surface expression also in the hepatoma Huh7 and HepG2 cells. Furthermore, H. pylori-induced HLA-C surface expression on AGS cells promoted inhibition of NK cells by KIR, and thereby protected AGS cells from NK cell cytotoxicity. These results suggest that H. pylori enhances HLA-C expression in host cells and protects them from the cytotoxic attack of NK cells expressing HLA-C-specific inhibitory receptors.
幽门螺杆菌（H. pylori）似乎在胃癌中起致病作用。H. pylori 也已在已确诊的胃癌中被检测到。H. pylori 如何调节对癌症的免疫反应尚不清楚。自然杀伤（NK）细胞对感染或恶性细胞的细胞毒性受其表面表达的激活和抑制受体的谱控制。在这里，我们研究了 H. pylori 诱导的 NK 细胞表面配体、激活和抑制受体表达的变化，在胃腺癌 AGS 细胞中，并研究了它们对 NK 细胞反应的影响。AGS 细胞缺乏或表面表达低水平的 I 类主要组织相容性复合物（MHC-I）分子 HLA-E 和 HLA-C-分别是主要 NK 细胞抑制受体 NKG2A 和杀伤细胞免疫球蛋白样受体（KIR）的配体。然而，AGS 细胞表面表达高水平的激活受体 DNAM-1 和 CD2 的配体，以及粘附分子 LFA-1。一致地，尽管 NK 细胞表达抑制性 KIR，但 AGS 细胞仍对 NK 细胞杀伤敏感。此外，H. pylori 增强了 AGS 细胞表面 HLA-C 的表达。H. pylori 感染增强了 HLA-C 蛋白的合成，这可以解释 H. pylori 诱导的 HLA-C 表面表达。H. pylori 感染还增强了肝癌 Huh7 和 HepG2 细胞表面 HLA-C 的表达。此外，H. pylori 在 AGS 细胞上诱导的 HLA-C 表面表达促进了 KIR 对 NK 细胞的抑制作用，从而保护 AGS 细胞免受 NK 细胞的细胞毒性攻击。这些结果表明，H. pylori 增强了宿主细胞中 HLA-C 的表达，并保护它们免受表达 HLA-C 特异性抑制受体的 NK 细胞的细胞毒性攻击。
