Intranasal immunisation with recombinant Toxoplasma gondii uridine phosphorylase confers resistance against acute toxoplasmosis in mice.

IF 2.3 2区 医学 Q2 PARASITOLOGY Parasite Pub Date : 2023-01-01 Epub Date: 2023-11-02 DOI:10.1051/parasite/2023047
Li-Tian Yin, Ying-Jie Ren, Yu-Jie You, Yong Yang, Zhi-Xin Wang, Hai-Long Wang
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Abstract

Toxoplasmosis is caused by Toxoplasma gondii, which infects all warm-blooded animals, including humans. Currently, control measures for T. gondii infection are insufficient due to the lack of effective medications or vaccines. In this paper, recombinant T. gondii uridine phosphorylase (rTgUPase) was expressed in Escherichia coli and purified via Ni2+-NTA agarose. rTgUPase was inoculated intranasally into BALB/c mice, and the induced immune responses were evaluated by mucosal and humoral antibody and cytokine assays and lymphoproliferative measurements. Moreover, the protective effect against the T. gondii RH strain infection was assessed by calculating the burdens of tachyzoites in the liver and brain and by recording the survival rate and time. Our results revealed that mice immunised with 30 μg rTgUPase produced significantly higher levels of secretory IgA (sIgA) in nasal, intestinal, vaginal and vesical washes and synthesised higher levels of total IgG, IgG1 and, in particular, IgG2a in their blood sera. rTgUPase immunisation increased the production of IFN-gamma, interleukin IL-2 and IL-4, but not IL-10 from isolated mouse spleen cells and enhanced splenocyte proliferation in vitro. rTgUPase-inoculated mice were effectively protected against infection with the T. gondii RH strain, showing considerable reduction of tachyzoite burdens in liver and brain tissues after 30 days of infection, and a 44.29% increase in survival rate during an acute challenge. The above findings show that intranasal inoculation with rTgUPase provoked mucosal, humoral and cellular immune responses and indicate that rTgUPase might serve as a promising vaccine candidate for protecting against toxoplasmosis.

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重组弓形虫尿苷磷酸化酶鼻内免疫可增强小鼠对急性弓形虫病的抵抗力。
弓形虫病是由弓形虫引起的,弓形虫感染所有温血动物,包括人类。目前,由于缺乏有效的药物或疫苗,弓形虫感染的控制措施不足。本文将重组弓形虫尿苷磷酸化酶(rTgUPase)在大肠杆菌中表达,并通过Ni2+-NTA琼脂糖纯化。将rTgUPase鼻内接种到BALB/c小鼠中,并通过粘膜和体液抗体、细胞因子测定和淋巴增殖测定来评估诱导的免疫反应。此外,通过计算肝和脑中速殖子的负担并记录存活率和时间来评估对弓形虫RH株感染的保护作用。我们的研究结果表明,用30μg rTgUPase免疫的小鼠在鼻腔、肠道、阴道和膀胱冲洗液中产生了显著更高水平的分泌型IgA(sIgA),并在其血清中合成了更高的总IgG、IgG1,特别是IgG2a。rTgUPase免疫增加了分离的小鼠脾细胞产生的IFN-γ、白细胞介素IL-2和IL-4,但不增加IL-10,并在体外增强了脾细胞的增殖。接种rTgUPase的小鼠被有效地保护免受弓形虫RH菌株的感染,在感染30天后,肝和脑组织中的速殖子负荷显著减少,在急性攻击期间存活率增加44.29%。上述发现表明,rTgUPase的鼻内接种引起了粘膜、体液和细胞免疫反应,并表明rTgUP酶可能是一种很有前途的预防弓形虫病的候选疫苗。
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来源期刊
Parasite
Parasite 医学-寄生虫学
CiteScore
5.50
自引率
6.90%
发文量
49
审稿时长
3 months
期刊介绍: Parasite is an international open-access, peer-reviewed, online journal publishing high quality papers on all aspects of human and animal parasitology. Reviews, articles and short notes may be submitted. Fields include, but are not limited to: general, medical and veterinary parasitology; morphology, including ultrastructure; parasite systematics, including entomology, acarology, helminthology and protistology, and molecular analyses; molecular biology and biochemistry; immunology of parasitic diseases; host-parasite relationships; ecology and life history of parasites; epidemiology; therapeutics; new diagnostic tools. All papers in Parasite are published in English. Manuscripts should have a broad interest and must not have been published or submitted elsewhere. No limit is imposed on the length of manuscripts, but they should be concisely written. Papers of limited interest such as case reports, epidemiological studies in punctual areas, isolated new geographical records, and systematic descriptions of single species will generally not be accepted, but might be considered if the authors succeed in demonstrating their interest.
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