Zhang Xianjuan, Wang Qing, Han Shuo, Song Guanghui, Wang Bin, Wang Yunyang
Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Spinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.
PLoS One. 2025 May 5;20(5):e0322334. doi: 10.1371/journal.pone.0322334. eCollection 2025.
Human cytomegalovirus (HCMV) has evolved sophisticated strategies to evade host immune defenses, enabling its persistent survival in human populations. HCMV intermediate-early protein 2 (IE2) has been identified as a crucial factor in immune evasion mechanisms. However, the specific immunomodulatory effects of IE2 on antigen presentation remain insufficiently explored. In this study, we established a transgenic mouse model to systematically examine the impact and molecular mechanisms of IE2 on macrophages (Mφs) antigen presentation in vivo. Our findings demonstrated that IE2 modifies Mφs' function by preventing their phagocytic activity and polarization. Additionally, IE2 inhibits Mφs overactivation both in vivo and in vitro, which raises IL-10 levels and activates the downstream mediator STAT3, which in turn decreases T cell immune responses by encouraging T helper 2 (Th2) type responses. In conclusion, these findings underscore the potential of IE2 as a critical regulator of immune evasion and may contribute to the development of novel, targeted therapeutic strategies against the virus.
人类巨细胞病毒（HCMV）已进化出复杂的策略来逃避宿主的免疫防御，使其能够在人群中持续存活。HCMV早期中间蛋白2（IE2）已被确定为免疫逃避机制中的关键因素。然而，IE2对抗抗原呈递的具体免疫调节作用仍未得到充分研究。在本研究中，我们建立了一个转基因小鼠模型，以系统地研究IE2在体内对巨噬细胞（Mφs）抗原呈递的影响及其分子机制。我们的研究结果表明，IE2通过阻止Mφs的吞噬活性和极化来改变其功能。此外，IE2在体内和体外均抑制Mφs的过度激活，这会提高IL-10水平并激活下游介质STAT3，进而通过促进辅助性T细胞2（Th2）型反应来降低T细胞免疫反应。总之，这些发现强调了IE2作为免疫逃避关键调节因子的潜力，并可能有助于开发针对该病毒的新型靶向治疗策略。
