Therapy modulates the response to T cell epitopes over the spectrum of tuberculosis infection

IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES
Linda Petrone , Daniela Peruzzu , Anna Maria Gerarda Altera , Andrea Salmi , Valentina Vanini , Gilda Cuzzi , Andrea Coppola , Valeria Mellini , Gina Gualano , Fabrizio Palmieri , Sudhasini Panda , Bjoern Peters , Alessandro Sette , Cecilia Sofie Lindestam Arlehamn , Delia Goletti
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引用次数: 0

Abstract

Background

Identifying stage-specific antigens is essential for developing tuberculosis (TB) diagnostics and vaccines. In a low TB endemic country, we characterized, the Mycobacterium tuberculosis (Mtb)-specific immune response to a pool of Mtb-derived epitopes (ATB116), demonstrated as associated with TB disease.

Methods

In this prospective observational cross-sectional study, we enrolled healthy donors (HD), subjects with TB disease, and TB infection (TBI) at baseline and therapy completion. T-cell response after whole blood stimulation with the peptide pools was characterized by ELISA, flow cytometry, and multiplex assay.

Results

ATB116-specific IFN-γ response (by ELISA) significantly associates with Mtb regardless of infection/disease (p < 0.0001) and decreases during TB therapy (p = 0.0002). Flow cytometry confirms that ATB116-specific CD4+ T-cell response associated with Mtb regardless of infection/disease (p < 0.0001) and shows a significantly higher frequency of IFN-γ/IL-2 and central memory T-cells in TBI compared to TB (p = 0.016; p = 0.0242, respectively). CD4+ T cell-specific response decreases after TB therapy completion. The antigen-specific CD8+ T-cell response mirrors the CD4+ response. Finally, the multiplex assay analysis showed that ATB116 induces several immune factors in both TB and TBI.

Conclusion

We characterized the immune response to Mtb peptide pools that is modulated by TB therapy. These results are important for our understanding of TB immunopathogenesis and vaccine design.
治疗可调节结核病感染范围内对 T 细胞表位的反应。
背景:确定阶段特异性抗原对于开发结核病(TB)诊断和疫苗至关重要。在一个结核病低流行的国家,我们研究了结核分枝杆菌(Mtb)特异性免疫反应的特征,该免疫反应与结核病相关:在这项前瞻性观察横断面研究中,我们招募了健康供体(HD)、结核病患者和结核感染者(TBI)在基线和治疗结束时进行研究。用酶联免疫吸附试验、流式细胞术和多重检测法鉴定了多肽池刺激全血后的 T 细胞反应:结果:无论感染/患病情况如何,ATB116 特异性 IFN-γ 反应(通过酶联免疫吸附试验)都与 Mtb 显著相关(p+ T 细胞反应与 Mtb 相关,无论感染/患病情况如何(p+ T 细胞特异性反应在结核病治疗完成后下降)。抗原特异性 CD8+ T 细胞反应反映了 CD4+ 反应。最后,多重检测分析表明,ATB116 在结核病和创伤性脑损伤中都能诱导多种免疫因子:我们描述了结核病治疗对 Mtb 多肽池免疫反应的调节。这些结果对于我们了解结核病的免疫发病机制和疫苗设计非常重要:在本研究中生成和/或分析的原始数据将在 INMI 机构资料库(rawdata.inmi.it)中提供,但需注册。从按发表年份排序的文章列表中选择感兴趣的文章,即可找到相关数据。访问数据无需付费。如果应用程序出现故障,可直接通过电子邮件将请求发送至 biblioteca@inmi.it。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Infection
Journal of Infection 医学-传染病学
CiteScore
45.90
自引率
3.20%
发文量
475
审稿时长
16 days
期刊介绍: The Journal of Infection publishes original papers on all aspects of infection - clinical, microbiological and epidemiological. The Journal seeks to bring together knowledge from all specialties involved in infection research and clinical practice, and present the best work in the ever-changing field of infection. Each issue brings you Editorials that describe current or controversial topics of interest, high quality Reviews to keep you in touch with the latest developments in specific fields of interest, an Epidemiology section reporting studies in the hospital and the general community, and a lively correspondence section.
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