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含CpG的寡脱氧核苷酸在抗弓形虫感染的保护作用中作用有限。

CpG-containing ODN has a limited role in the protection against Toxoplasma gondii.

作者信息

Saavedra R, Leyva R, Tenorio E P, Haces M L, Rodríguez-Sosa M, Terrazas L I, Hérion P

机构信息

Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico.

出版信息

Parasite Immunol. 2004 Feb;26(2):67-73. doi: 10.1111/j.0141-9838.2004.00684.x.

Abstract

Bacterial DNA containing immunostimulatory motifs (CpG) induces the development of a T(H1) immune response. Since protection against Toxoplasma gondii is correlated with this type of response, the aim of this work was to determine if a synthetic oligodeoxynucleotide (ODN) containing CpG sequences could be useful as adjuvant for the induction of a long-lasting protective immune response against T. gondii. BALB/c mice immunized with a total soluble antigen of T. gondii (TSA2) mixed with ODN-containing CpG sequences developed a typical TH1 response, as determined by antibody isotypes and interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) production by spleen cells. However, they did not resist a challenge with the virulent RH strain of the parasite. Absence of protection paralleled with lower levels of IFN-gamma, when compared with mice vaccinated with the live tachyzoites of the attenuated ts.4 strain of the parasite, which resisted this challenge. Intraperitoneal injection of ODN alone to mice induced a high degree of resistance to a lethal challenge inoculated by the same route. Nevertheless, this nonspecific protection was transient. Thus, the use of ODN containing CpG motifs as adjuvant is of limited value for the induction of a protective immune response against T. gondii.

摘要

含有免疫刺激基序(CpG)的细菌DNA可诱导T(H1)免疫反应的产生。由于针对刚地弓形虫的保护作用与此类反应相关,因此本研究的目的是确定含有CpG序列的合成寡脱氧核苷酸(ODN)是否可用作佐剂,以诱导针对刚地弓形虫的持久保护性免疫反应。用刚地弓形虫的总可溶性抗原(TSA2)与含CpG序列的ODN混合免疫BALB/c小鼠,通过抗体亚型以及脾细胞产生的干扰素-γ(IFN-γ)和白细胞介素-4(IL-4)来确定,这些小鼠产生了典型的TH1反应。然而,它们无法抵抗该寄生虫的强毒株RH株的攻击。与接种减毒ts.4株寄生虫活速殖子的小鼠相比,缺乏保护作用与较低水平的IFN-γ相关,后者能够抵抗这种攻击。单独向小鼠腹腔注射ODN可诱导其对通过相同途径接种的致死性攻击产生高度抗性。然而,这种非特异性保护是短暂的。因此,使用含CpG基序的ODN作为佐剂诱导针对刚地弓形虫的保护性免疫反应的价值有限。

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