In-vivo expressed Mycobacterium tuberculosis antigens recognised in three mouse strains after infection and BCG vaccination.
In-vivo expressed Mycobacterium tuberculosis antigens recognised in three mouse strains after infection and BCG vaccination.
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DOI：
10.1038/s41541-021-00343-2
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发表时间：
2021-06-03
期刊：
影响因子：
9.2
通讯作者：
Ottenhoff THM
中科院分区：
文献类型：
--
作者：
Coppola M;Jurion F;van den Eeden SJF;Tima HG;Franken KLMC;Geluk A;Romano M;Ottenhoff THM
新型结核病(TB)疫苗优选应当(i)增强由先前的BCG疫苗接种诱导的宿主免疫应答，并且(ii)针对在整个Mtb感染周期中表达的结核分枝杆菌(Mtb)蛋白。人类 Mtb 抗原发现筛选鉴定了在小鼠体内感染期间高表达的 Mtb 基因编码的抗原（IVE-TB 抗原）。为了将这些发现转化为动物模型，我们在三种不同的小鼠品系中确定了 Mtb 攻击或 BCG 疫苗接种后 T 细胞识别哪些 IVE-TB 抗原。在结核病抗药性和易感性小鼠中发现了 11 种 Mtb 抗原。证实了之前的人类数据，几种 Mtb 抗原诱导了除 IFN-γ 之外的细胞因子。易感 C3HeB/FeJ 小鼠的肺细胞产生较少的 TNF-α，与结核病易感表型一致。此外，BCG 在 C3HeB/FeJ 小鼠中诱导了对多种抗原的反应，提供了加强的潜力。因此，对人类中鉴定出的有希望的结核分枝杆菌抗原的识别在结核病敏感性差异很大的多种小鼠结核病感染模型中得到了验证。这提供了评估 IVE-TB 抗原作为诊断和疫苗抗原的转化工具。
Novel tuberculosis (TB)-vaccines preferably should (i) boost host immune responses induced by previous BCG vaccination and (ii) be directed against Mycobacterium tuberculosis (Mtb) proteins expressed throughout the Mtb infection-cycle. Human Mtb antigen-discovery screens identified antigens encoded by Mtb-genes highly expressed during in vivo murine infection (IVE-TB antigens). To translate these findings towards animal models, we determined which IVE-TB-antigens are recognised by T-cells following Mtb challenge or BCG vaccination in three different mouse strains. Eleven Mtb-antigens were recognised across TB-resistant and susceptible mice. Confirming previous human data, several Mtb-antigens induced cytokines other than IFN-γ. Pulmonary cells from susceptible C3HeB/FeJ mice produced less TNF-α, agreeing with the TB-susceptibility phenotype. In addition, responses to several antigens were induced by BCG in C3HeB/FeJ mice, offering potential for boosting. Thus, recognition of promising Mtb-antigens identified in humans validates across multiple mouse TB-infection models with widely differing TB-susceptibilities. This offers translational tools to evaluate IVE-TB-antigens as diagnostic and vaccine antigens.
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影响因子：
4.6
作者：
Coppola M;van Meijgaarden KE;Franken KL;Commandeur S;Dolganov G;Kramnik I;Schoolnik GK;Comas I;Lund O;Prins C;van den Eeden SJ;Korsvold GE;Oftung F;Geluk A;Ottenhoff TH
通讯作者：
Ottenhoff TH
影响因子：
4.8
作者：
Corrales, Rosa Milagros;Molle, Virginie;Kremer, Laurent
通讯作者：
Kremer, Laurent
影响因子：
5.2
作者：
Serra-Vidal MM;Latorre I;Franken KL;Díaz J;de Souza-Galvão ML;Casas I;Maldonado J;Milà C;Solsona J;Jimenez-Fuentes MÁ;Altet N;Lacoma A;Ruiz-Manzano J;Ausina V;Prat C;Ottenhoff TH;Domínguez J
通讯作者：
Domínguez J
影响因子：
64.8
作者：
Famelis, Nikolaos;Rivera-Calzada, Angel;Geibel, Sebastian
通讯作者：
Geibel, Sebastian
BCG 分泌的 O-甘露糖化蛋白的鉴定以及免疫显性抗原 BCG_0470 和 BCG_0980 的表征
影响因子：
5.2
作者：
Deng, Guoying;Zhang, Wenli;Yang, Shufeng
通讯作者：
Yang, Shufeng