Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, No. 518, Ziyue Road, Shanghai 200241, China.
State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China.
Sci Rep. 2016 Sep 20;6:33815. doi: 10.1038/srep33815.
Tumor suppressor p53 is involved in regulating immune responses, which contribute to antitumor and antiviral activity. However, whether p53 has anti-bacterial functions remains unclear. Listeria monocytogenes (LM) causes listeriosis in humans and animals, and it is a powerful model for studying innate and adaptive immunity. In the present study, we illustrate an important regulatory role of p53 during LM infection. p53 knockout (p53KO) mice were more susceptible to LM infection, which was manifested by a shorter survival time and lower survival rate. p53KO mice showed significant impairments in LM eradication. Knockdown of p53 in RAW264.7 and HeLa cells resulted in increased invasion and intracellular survival of LM. Furthermore, the invasion and intracellular survival of LM was inhibited in p53-overexpressing RAW264.7 and HeLa cells. LM-infected p53KO mice exhibited severe clinical symptoms and organ injury, presumably because of the abnormal production of the pro-inflammatory cytokines TNF-α, IL-6, IL-12, and IL-18. Decreased IFN-γ and GBP1 productions were observed in LM-infected p53-deficient mice or cells. The combination of these defects likely resulted in the overwhelming LM infection in the p53KO mice. These observations indicate that p53 serves as an important regulator of the host innate immune that protects against LM infection.
肿瘤抑制因子 p53 参与调节免疫反应，有助于抗肿瘤和抗病毒活性。然而，p53 是否具有抗细菌功能尚不清楚。李斯特菌（LM）在人类和动物中引起李斯特菌病，是研究先天和适应性免疫的有力模型。在本研究中，我们说明了 p53 在 LM 感染过程中的重要调节作用。p53 敲除（p53KO）小鼠对 LM 感染更敏感，表现为存活时间更短，存活率更低。p53KO 小鼠在 LM 清除方面存在明显缺陷。在 RAW264.7 和 HeLa 细胞中敲低 p53 导致 LM 侵袭和细胞内存活增加。此外，p53 过表达 RAW264.7 和 HeLa 细胞中 LM 的侵袭和细胞内存活受到抑制。感染 LM 的 p53KO 小鼠表现出严重的临床症状和器官损伤，可能是由于促炎细胞因子 TNF-α、IL-6、IL-12 和 IL-18 的异常产生。在 LM 感染的 p53 缺陷小鼠或细胞中观察到 IFN-γ和 GBP1 产生减少。这些缺陷的结合可能导致 p53KO 小鼠中 LM 感染的压倒性。这些观察结果表明，p53 是宿主先天免疫的重要调节剂，可防止 LM 感染。
