强烈的先天和适应性免疫应答都是针对红细胞内原生动物寄生虫的保护的重要组成部分。对牛babesiosis的抗性与干扰素(IFN)-γ介导的反应有关。CD4+T细胞和巨噬细胞已被鉴定为介导病原体清除的主要效应细胞。以前,发现顶膜抗原1(AMA-1)显着诱导免疫应答,抑制牛裂殖子的生长和侵袭。然而,针对牛芽孢杆菌AMA-1(BbAMA-1)结构的体液和细胞免疫应答的详细表征尚未建立。在这里,本研究旨在表达重组BbAMA-1结构域I+II蛋白[rBbAMA-1(I/II)],这是最主要的免疫反应区域,并表征其免疫反应。因此,与对照组相比,接种BbAMA-1(I/II)的牛显着发展出高滴度的总免疫球蛋白(Ig)G抗体和高比例的IgG2/IgG1。有趣的是,我们研究中产生的基于BbAMA-1(I/II)的制剂可以诱导产生IFN-γ和肿瘤坏死因子(TNF)-α的CD4T细胞和CD8T细胞。总的来说,结果表明,用BbAMA-1(I/II)免疫牛可以诱导强烈的Th1细胞反应。为了支持这一点,我们观察到Th1细胞因子mRNA转录本的上调,包括IFN-γ,TNF-α,白细胞介素(IL)-2和IL-12,与IL-4、IL-6和IL-10的下调相反,这将指示Th2细胞因子应答。此外,观察到诱导型一氧化氮合酶(iNOS)的上调。总之,这是关于BbAMA-1应答的深入免疫学特征的首次报道.根据我们的结果,BbAMA-1被认为是针对牛芽孢杆菌感染的潜在候选疫苗。Th1细胞反应证明,它可能提供保护性免疫。然而,需要在免疫的牛中进一步攻击-暴露于强毒株。以确定其保护功效。
Both strong innate and adaptive immune responses are an important component of protection against intraerythrocytic protozoan parasites. Resistance to bovine babesiosis is associated with interferon (IFN)-γ mediated responses. CD4+ T cells and macrophages have been identified as major effector cells mediating the clearance of pathogens. Previously, the apical membrane antigen 1 (AMA-1) was found to significantly induce the immune response inhibiting B. bovis merozoite growth and invasion. However, a detailed characterization of both humoral and cellular immune responses against the structure of B. bovis AMA-1 (BbAMA-1) has not yet been established. Herein, the present study aimed to express the recombinant BbAMA-1 domain I+II protein [rBbAMA-1(I/II)], which is the most predominant immune response region, and to characterize its immune response. As a result, cattle vaccinated with BbAMA-1(I/II) significantly developed high titters of total immunoglobulin (Ig) G antibodies and a high ratio of IgG2/IgG1 when compared to control groups. Interestingly, the BbAMA-1(I/II)-based formulations produced in our study could elicit CD4+ T cells and CD8+ T cells producing IFN-γ and tumor necrosis factor (TNF)-α. Collectively, the results indicate that immunization of cattle with BbAMA-1(I/II) could induce strong Th1 cell responses. In support of this, we observed the up-regulation of Th1 cytokine mRNA transcripts, including IFN-γ, TNF-α, Interleukin (IL)-2 and IL-12, in contrast to down regulation of IL-4, IL-6 and IL-10, which would be indicative of a Th2 cytokine response. Moreover, the up-regulation of inducible nitric oxide synthase (iNOS) was observed. In conclusion, this is the first report on the in-depth immunological characterization of the response to BbAMA-1. According to our results, BbAMA-1 is recognized as a potential candidate vaccine against B. bovis infection. As evidenced by the Th1 cell response, it could potentially provide protective immunity. However, further challenge-exposure with virulent B. bovis strain in immunized cattle would be needed to determine its protective efficacy.