Contribution of the CD153/CD30 axis to Mycobacterium tuberculosis control in humans

CD153/CD30 轴对人类结核分枝杆菌控制的贡献

• 批准号: 9981646
• 负责人: Catherine Riou
• 金额: $ 11.46万
• 依托单位: UNIVERSITY OF CAPE TOWN
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-23 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9981646
• 关键词: Address; Affect; Agonist; Blood specimen; Bronchoalveolar Lavage; CD30L; CD4 Positive T Lymphocytes; Cells; Clinical; Clinical/Radiologic; Communicable Diseases; Data; Development; Disease; Disease Progression; Equilibrium; Expression Profiling; Family; Flow Cytometry; Frequencies; Granuloma; HIV; HIV Infections; Human; Immune; Immune response; Immunologic Factors; Individual; Infection Control; Interferon Type II; Investigation; Knowledge; Lead; Liquid substance; Lung; Lung Inflammation; Measures; Mediating; Metabolic; Modeling; Monitor; Mus; Mycobacterium tuberculosis; Nature; PET/CT scan; Pathway interactions; Patients; Pattern; Pericardial body location; Persons; Phenotype; Pleural; Pulmonary Tuberculosis; Respiratory physiology; Role; Severity of illness; Signal Transduction; Site; T cell response; T-Cell Depletion; TNF gene; TNFRSF8 gene; Testing; Tissues; Tuberculosis; Tuberculosis Vaccines; biobank; clinical development; cohort; cytokine; design; efficacy testing; experimental study; fluorodeoxyglucose; fluorodeoxyglucose positron emission tomography; insight; macrophage; mouse model; nonhuman primate; novel; novel strategies; novel vaccines; peripheral blood; receptor; response; synergism; tool; tuberculosis immunity; tuberculosis treatment

PROJECT SUMMARY In 90% of cases, healthy persons infected with Mycobacterium tuberculosis (Mtb) remain asymptomatic. This implies that the host generates and maintains a partially protective immune response capable of containing bacterial replication. When this equilibrium is altered, such as during HIV-associated CD4 T cell depletion, TB disease can occur. However, the precise nature of Mtb-specific CD4+ T cells that confer immune protection remains elusive, hindering the development of new vaccines. It is now clearly established that while necessary, IFNγ is not sufficient to provide lung protection to Mtb. The recent finding, in a mouse model, that the TNF superfamily molecule CD153 confers partial protection for pulmonary Mtb infection (in an IFNγ- independent manner) reveals a new avenue to potentially identify an important immune correlate of protection to Mtb in humans. In ongoing experiments, we have found that Mtb-specific CD4+ T cells from individuals with latent TB infection (LTBI) express CD153 and that the expression of this molecule was significantly reduced in patients with active TB disease. Additionally, in TB asymptomatic persons with evidence of TB related lung inflammation measured using PET/CT, CD153 expression in Mtb-specific CD4 T cells negatively associates with lung metabolic activity. These findings strongly suggest that CD153, along with IFNg, may be required to confer optimal protection against pulmonary Mtb infection in humans. To better understand the role of CD153 (and its receptor, CD30) for Mtb protection, we will: 1) comprehensively characterize Mtb-specific CD153+ CD4 T cells during latent and active TB, both in peripheral blood and at sites of TB diseases; 2) define the impact of HIV infection on Mtb-specific CD4 T cells expressing CD153 and 3) investigate the mechanisms of action of the CD153/CD30 pathway in response to Mtb. This study will 1) enhance our understanding of immune mechanisms required for human TB protection and 2) identify novel mechanisms by which HIV infection alters these immune responses. This project could lead to the development of new tools to monitor the efficacy of novel TB vaccines.

项目总结

项目成果

Rapid, simplified whole blood-based multiparameter assay to quantify and phenotype SARS-CoV-2-specific T-cells.

• DOI: 10.1183/13993003.00285-2021
• 发表时间: 2022-01
• 期刊: The European respiratory journal
• 作者: Riou C;Schäfer G;du Bruyn E;Goliath RT;Stek C;Mou H;Hung D;Wilkinson KA;Wilkinson RJ
• 通讯作者: Wilkinson RJ

Distinct T cell polyfunctional profile in SARS-CoV-2 seronegative children associated with endemic human coronavirus cross-reactivity.

• DOI: 10.1016/j.isci.2023.108728
• 发表时间: 2024-01-19
• 期刊: ISCIENCE
• 影响因子: 5.8
• 作者: Benede, Ntombi;Tincho, Marius B.;Walters, Avril;Subbiah, Vennesa;Ngomti, Amkele;Baguma, Richard;Butters, Claire;Hahnle, Lina;Mennen, Mathilda;Skelem, Sango;Adriaanse, Marguerite;Facey-Thomas, Heidi;Scott, Christiaan;Day, Jonathan;Spracklen, Timothy F.;van Graan, Strauss;Balla, Sashkia R.;Moyo-Gwete, Thandeka;Moore, Penny L.;MacGinty, Rae;Botha, Maresa;Workman, Lesley;Johnson, Marina;Goldblatt, David;Zar, Heather J.;Ntusi, Ntobeko A. B.;Zuhlke, Liesl;Webb, Kate;Riou, Catherin;Burgers, Wendy A.;Keeton, Roanne S.
• 通讯作者: Keeton, Roanne S.

Impact of SARS-CoV-2 exposure history on the T cell and IgG response.

• DOI: 10.1016/j.xcrm.2022.100898
• 发表时间: 2023-01-17
• 期刊: CELL REPORTS MEDICINE
• 影响因子: 14.3
• 作者: Keeton, Roanne;Tincho, Marius B.;Suzuki, Akiko;Benede, Ntombi;Ngomti, Amkele;Baguma, Richard;Chauke, Masego, V;Mennen, Mathilda;Skelem, Sango;Adriaanse, Marguerite;Grifoni, Alba;Weiskopf, Daniela;Sette, Alessandro;Bekker, Linda -Gail;Gray, Glenda;Ntusi, Ntobeko A. B.;Burgers, Wendy A.;Riou, Catherine
• 通讯作者: Riou, Catherine

Homologous Ad26.COV2.S vaccination results in reduced boosting of humoral responses in hybrid immunity, but elicits antibodies of similar magnitude regardless of prior infection.

同源 Ad26.COV2.S 疫苗接种会导致混合免疫中体液反应的增强减弱，但无论先前是否感染，都会引发相似程度的抗体。

• DOI: 10.1101/2023.03.15.23287288
• 发表时间: 2023
• 期刊: medRxiv : the preprint server for health sciences
• 作者: Moyo-Gwete,Thandeka;Richardson,SimoneI;Keeton,Roanne;Hermanus,Tandile;Spencer,Holly;Manamela,NeliaP;Ayres,Frances;Makhado,Zanele;Motlou,Thopisang;Tincho,MariusB;Benede,Ntombi;Ngomti,Amkele;Baguma,Richard;Chauke,MasegoV;Menn
• 通讯作者: Menn