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
{"title":"Therapy modulates the response to T cell epitopes over the spectrum of tuberculosis infection","authors":"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","doi":"10.1016/j.jinf.2024.106295","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Identifying stage-specific antigens is essential for developing tuberculosis (TB) diagnostics and vaccines. In a low TB endemic country, we characterized, the <em>Mycobacterium tuberculosis</em> (Mtb)-specific immune response to a pool of Mtb-derived epitopes (ATB116), demonstrated as associated with TB disease.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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<sup>+</sup> 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<sup>+</sup> T cell-specific response decreases after TB therapy completion. The antigen-specific CD8<sup>+</sup> T-cell response mirrors the CD4<sup>+</sup> response. Finally, the multiplex assay analysis showed that ATB116 induces several immune factors in both TB and TBI.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3000,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Infection","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0163445324002299","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
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.
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.