Early Kinetics of Intestinal Infection and Immune Responses to Two Toxoplasma gondii Strains in Pigs

Early Kinetics of Intestinal Infection and Immune Responses to Two Toxoplasma gondii Strains in Pigs
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DOI:
10.3389/fcimb.2020.00161
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发表时间:
2020-04-16
影响因子:
5.7
通讯作者:
Cox, Eric
Cox, Eric
中科院分区:
医学2区
文献类型:
--
作者:
Rahman, Mizanur;Devriendt, Bert;Cox, Eric

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刚地弓形虫是一种专性细胞内寄生虫,主要通过摄入被(卵)囊污染的食物或水感染所有恒温动物。最近,我们观察到猪感染后弓形虫菌株特异性的组织清除情况:虽然适应猪的LR菌株在猪组织中持续存在,但随后感染人源的刚地菌株后,几种组织中的寄生虫被清除。我们假设感染后不久的肠道免疫反应可能在这种菌株特异性清除中起作用。为了评估这种可能性,我们在猪口服接种两种菌株的组织囊后2、4、8、14和28天,评估了小肠淋巴结细胞和血液免疫细胞中的寄生虫负荷以及这些细胞分泌的干扰素γ。有趣的是,接种LR菌株后第4天,仅在十二指肠淋巴结细胞中通过定量聚合酶链反应(qPCR)检测到寄生虫,而在空肠和回肠淋巴结细胞以及外周血单个核细胞(PBMCs)中,从接种后第8天开始才检测到寄生虫。尽管我们在接种刚地菌株后观察到类似的情况,但所检测细胞中的寄生虫负荷要低得多。这反映在接种后第28天,与刚地菌株感染的猪相比,LR菌株感染的猪的弓形虫特异性血清IgG反应显著更高。出乎意料的是,这在细胞再次刺激后的干扰素γ分泌中没有体现,两组中观察到的干扰素γ分泌几乎相等。总之,我们的结果表明,弓形虫首先在十二指肠进入宿主,然后可能从该部位传播到其他组织。早期免疫反应如何影响寄生虫从组织中的清除需要进一步研究。
Toxoplasma gondii is an obligate intracellular parasite, able to infect all homeothermic animals mostly through ingestion of (oo)cysts contaminated food or water. Recently, we observed a T. gondii strain-specific clearance from tissues upon infection in pigs: while the swine-adapted LR strain persisted in porcine tissues, a subsequent infection with the human-isolated Gangji strain cleared parasites from several tissues. We hypothesized that intestinal immune responses shortly after infection might play a role in this strain-specific clearance. To assess this possibility, the parasite load in small intestinal lymph node cells and blood immune cells as well as the IFN gamma secretion by these cells were evaluated at 2, 4, 8, 14, and 28 days post oral inoculation of pigs with tissue cysts of both strains. Interestingly, at day 4 post inoculation with the LR strain the parasite was detected by qPCR only in the duodenal lymph node cells, while in the jejunal and ileal lymph node cells and PBMCs the parasite was detected from day 8 post inoculation onwards. Although we observed a similar profile upon inoculation with the Gangji strain, the parasite load in the examined cells was much lower. This was reflected in a significantly higher T. gondii-specific serum IgG response in LR compared to Gangji infected pigs at day 28 post inoculation. Unexpectedly, this was not reflected in the IFN gamma secretion upon re-stimulation of the cells where almost equal IFN gamma secretion was observed in both groups. In conclusion, our results show that T. gondii first enters the host at the duodenum and then probably disseminates from this site to the other tissues. How the early immune response influences the clearance of parasite from tissues needs further study.