为探讨单增李斯特菌(Lisetria monocytogenes, LM)诱导小鼠滋养层细胞炎性体激活在其致小鼠流产中的作用,在体外用LM处理小鼠滋养层细胞,观察LM在细胞内的分布,检测培养基中白细胞介素(interleukin,IL)-1β水平和细胞裂解液中天冬氨酸蛋白水解酶1(cysteinyl aspartate specific proteinase 1,caspase 1)成熟片段水平以及乳酸脱氢酶(lactate dehydrogenase,LDH)释放量.结果显示:LM分布在细胞核周围,LM感染组细胞培养基中IL-1β水平、细胞裂解液中caspase 1成熟片段水平以及LDH释放量与对照组相比明显增加,溶血素O(listeriolysin O,LLO)缺陷型LM(Δhly LM)感染组IL-1β水平和caspase 1成熟片段水平明显低于野生型LM感染组.因此推测,LM可通过LLO诱导小鼠滋养层细胞炎性体的激活进而诱导IL-1β的分泌和滋养层细胞焦亡导致流产的发生,这可为临床防治LM诱导的流产提供科学依据.
To explore the role of Lisetria monocytogenes(LM)-induced mouse trophoblastic cell inflammasome activation in LM-induced mouse abortion, mouse trophoblastic cells were infected with LM. After the mouse trophoblastic cells were infected with LM in vitro,distribution of LM were observed. Interleukin(IL)-1β level in cell medium, cleavaged cysteinyl aspartate specific proteinase 1(caspase 1)level in the cell lysate and the amount of lactate dehydrogenase(LDH)release were detected. Results showed that LM distributed around the cell nucleus. Both IL-1β level in cell medium, cleavaged caspase 1 level in the cell lysate and the amount of LDH release were increased significantly in LM-infected group compared to control group, while the IL-1β level and the cleavaged caspase 1 level of the listeriolysin O(LLO)-deficient LM(Δ hly LM)-infected group were obviously lower than that of wild LM-infected group. Therefore, it is speculated that LM can activiate mouse trophoblastic inflammasome by LLO and promote the secretion of IL-1β and the pyrotosis of trophoblastic cells, which induced the mouse abortion. These results can provide a scientific basis for the clinical prevention and treatment on LM-induced abortion.
[1] DUAN R, XU X, WANG X, et al. Perinatal outcome in women with bacterial sepsis: A cross-sectional study from West China[J]. Medicine(Baltimore), 2019, 98(44): e17751. DOI:10.1097/md.0000000000017751.
[2] 李文艳,张娜,李晓宁,等.单增李斯特菌致流产小鼠子宫中Th1和Th2细胞因子的变化[J]. 河北大学学报(自然科学版), 2020, 40(1): 57-62. DOI:10.3969/j.issn.1000-1565.2020.01.009.
[3] LI W Y, CHANG Y M, LIANG S, et al. NLRP3 inflammasome activation contributes to Listeria monocytogenes-induced animal pregnancy failure[J]. BMC Vet Res, 2016, 12: 36. DOI:10.1186/s12917-016-0655-2.
[4] STAUD F, KARAHODA R. Trophoblast: The central unit of fetal growth, protection and programming[J]. Int J Biochem Cell Biol, 2018, 105: 35-40. DOI:10.1016/j.biocel.2018.09.016.
[5] REIS A S, REIS A S, BARBOZA R, et al. Inflammasome activation and IL-1 signaling during placental malaria induce poor pregnancy outcomes[J]. Sci Adv, 2020, 6(10): eaax6346. DOI:10.1126/sciadv.aax6346.
[6] YANG F, ZHENG Q, JIN L. Dynamic function and composition changes of immune cells during normal and pathological pregnancy at the maternal-fetal interface[J]. Front Immunol, 2019, 10: 2317. DOI:10.3389/fimmu.2019.02317.
[7] RATHINAM V A K, FITZGERALD K A. Inflammasome complexes: emerging mechanisms and effector functions[J]. Cell, 2016, 165(4): 792-800. DOI:10.1016/j.cell.2016.03.046.
[8] KELLEY N, JELTEMA D, DUAN Y H, et al. The NLRP3 inflammasome: an overview of mechanisms of activation and regulation[J]. Int J Mol Sci, 2019, 20(13): 3328. DOI:10.3390/ijms20133328.
[9] MEGLI C, MOROSKY S, RAJASUNDARAM D, et al. Inflammasome signaling in human placental trophoblasts regulates immune defense against Listeria monocytogenes infection[J]. J Exp Med, 2021, 218(1): e20200649. DOI:10.1084/jem.20200649.
[10] 周敏. 单增李斯特菌诱导滋养细胞NLRP3炎性体活化[D]. 长春: 吉林大学, 2015.
[11] VÉLEZ C, CLAUZURE M, WILLIAMSON D, et al. IL-1β, IL-2 and IL-4 concentration during porcine gestation[J]. Theriogenology, 2019, 128: 133-139. DOI:10.1016/j.theriogenology.2019.01.017.
[12] MALYSHKINA A I, SOTNIKOVA N Y, KROSHKINA N V, et al. Peculiarities of the content of peripheral blood cytokines in pregnant women with a habitual miscarriage.[J]. Klin Lab Diagn, 2020, 65(5): 299-303. DOI:10.18821/0869-2084-2020-65-5-299-303.
[13] ATIA T A. Placental apoptosis in recurrent miscarriage[J]. Kaohsiung J Med Sci, 2017, 33(9): 449-452. DOI:10.1016/j.kjms.2017.06.012.
[14] HASHINO M, TACHIBANA M, NISHIDA T, et al. Inactivation of the MAPK signaling pathway by Listeria monocytogenes infection promotes trophoblast giant cell death[J]. Front Microbiol, 2015, 6: 1145. DOI:10.3389/fmicb.2015.01145. (
