Hydrophobic Mycobacterial Antigens Elicit Polyfunctional T Cells in Mycobacterium bovis Immunized Cattle: Association With Protection Against Challenge?
Hydrophobic Mycobacterial Antigens Elicit Polyfunctional T Cells in Mycobacterium bovis Immunized Cattle: Association With Protection Against Challenge?
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DOI：
10.3389/fimmu.2020.588180
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发表时间：
2020
影响因子：
7.3
通讯作者：
Connelley T
中科院分区：
文献类型：
--
作者：
Benedictus L;Steinbach S;Holder T;Bakker D;Vrettou C;Morrison WI;Vordermeier M;Connelley T
牛结核病 (bTB) 由牛分枝杆菌引起，是一种牛的慢性疾病，对食品质量和生产产生不利影响。 bTB 疫苗的研究主要集中在蛋白质抗原上。然而，分枝杆菌具有厚而复杂的脂质外层，脂质和脂肽对于免疫逃避和毒力很重要。在人类中，结核分枝杆菌的脂质提取物已被证明可在体外引发有效对抗结核分枝杆菌的免疫反应。将氯仿-甲醇提取物(CME)应用于牛支原体BCG，以获得含有脂质和脂肽的疏水性抗原提取物(CMEbcg)。 CMEbcg 刺激 IFN-γ+IL-2+ 和 IL-17A+IL-22+ 多功能 T 细胞，并在接种 BCG 的牛分枝杆菌和攻击牛分枝杆菌的小牛中引发具有 Th1 和 Th17 细胞因子释放谱的 T 细胞反应。脂肽被证明是 CMEbcg 中的免疫显性抗原，通过 MHC II 类刺激 CD4 T 细胞。 CMEbcg 扩增的 T 细胞杀死 CMEbcg 负载的单核细胞，并且牛分枝杆菌 BCG 疫苗接种后的 CMEbcg 特异性 CD3 T 细胞增殖反应是牛分枝杆菌攻击后病理减少的最佳预测因子。尽管 CMEbcg 特异性免疫反应的高预测价值并不能证实与牛分枝杆菌攻击的保护之间存在因果关系，但当考虑到 CMEbcg 特异性 T 细胞的体外抗分枝杆菌表型（例如 Th1/Th17 细胞因子谱）时，这表明 CMEbcg 特异性免疫反应可以在针对牛分枝杆菌的免疫中发挥功能性作用。基于这些发现，我们得出结论，牛分枝杆菌脂肽是潜在的新型亚单位疫苗候选者，并且有必要进一步研究脂肽特异性免疫反应的功能特征及其在预防牛结核病中的作用。
Bovine tuberculosis (bTB), caused by Mycobacterium bovis, is a chronic disease of cattle with a detrimental impact on food quality and production. Research on bTB vaccines has predominantly been focused on proteinaceous antigens. However, mycobacteria have a thick and intricate lipid outer layer and lipids as well as lipopeptides are important for immune-evasion and virulence. In humans, lipid extracts of M. tuberculosis have been shown to elicit immune responses effective against M. tuberculosis in vitro. Chloroform-methanol extraction (CME) was applied to M. bovis BCG to obtain a hydrophobic antigen extract (CMEbcg) containing lipids and lipopeptides. CMEbcg stimulated IFN-γ+IL-2+ and IL-17A+IL-22+ polyfunctional T cells and elicited T cell responses with a Th1 and Th17 cytokine release profile in both M. bovis BCG vaccinated and M. bovis challenged calves. Lipopeptides were shown to be the immunodominant antigens in CMEbcg, stimulating CD4 T cells via MHC class II. CMEbcg expanded T cells killed CMEbcg loaded monocytes and the CMEbcg-specific CD3 T cell proliferative response following M. bovis BCG vaccination was the best predictor for reduced pathology following challenge with M. bovis. Although the high predictive value of CMEbcg-specific immune responses does not confirm a causal relationship with protection against M. bovis challenge, when taking into account the in vitro antimycobacterial phenotype of CMEbcg-specific T cells (e.g. Th1/Th17 cytokine profile), it is indicative that CMEbcg-specific immune responses could play a functional role in immunity against M. bovis. Based on these findings we conclude that lipopeptides of M. bovis are potential novel subunit vaccine candidates and that further studies into the functional characterization of lipopeptide-specific immune responses together with their role in protection against bovine tuberculosis are warranted.
影响因子：
3.7
作者：
Nguyen TK;Reinink P;El Messlaki C;Im JS;Ercan A;Porcelli SA;Van Rhijn I
通讯作者：
Van Rhijn I