The Role of Sex Steroid Hormones in CD4+ T Cell-mediated Immune Responses to Tuberculosis

性类固醇激素在 CD4 T 细胞介导的结核病免疫反应中的作用

• 批准号: 10655729
• 负责人: DJENEBA DABITAO
• 金额: $ 5.04万
• 依托单位: UNIV OF SCIENCES, TECH & TECH OF BAMAKO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10655729
• 关键词: Antigens; Automobile Driving; Award; Biological; CD4 Positive T Lymphocytes; COVID-19 pandemic; Cells; Clinical Research; Epidemiology; Estradiol; Female; Flow Cytometry; Genus Mycobacterium; Gonadal Steroid Hormones; Immune; Immune response; International; K-Series Research Career Programs; Laboratories; Mali; Outcome; Parents; Pulmonary Tuberculosis; Reagent; Research Activity; Research Project Grants; Role; Sex Differences; Testosterone; Training; Training Activity; Travel; Tuberculosis; Universities; Vendor; Woman; cell mediated immune response; cost; design; experimental study; laboratory experience; laboratory experiment; male; men; research study; sex; success

Abstract A large body of evidence indicates that males are more likely to develop active pulmonary tuberculosis (TB) than females. However, research studies on this theme have been primarily focused on characterizing the epidemiology of TB in a sex-specific manner with little to no exploration of the biological mechanisms driving sex differences in TB outcomes. For this reason, in 2019, I have initiated a research project as part of a career development award (K43TW011426) to investigate the role of sex steroid hormones, namely testosterone and estradiol, on immune responses to tuberculosis. During the beginning of this project, I was directly impacted by unforeseen challenges, including COVID-19 pandemic and prolonged crisis in Mali, which led to an inability to travel to the US for experiential training and procure reagents and supplies from international vendors at regular costs. I am now proposing supplemental activities, including laboratory training and experiments to be conducted both at the Johns Hopkins University and the University Clinical Research Center (UCRC) in Mali. The activities include multiparameter flow cytometry and co-treatment of immune cells with mycobacterium antigens and sex steroid hormones ex vivo prior acquisition by flow cytometry. These activities were carefully designed to directly respond to the urgent need of finishing the experiments proposed in the parent award and increase the likelihood of success in applying for an R-type application next year.

抽象的 大量证据表明男性更容易患活动性肺结核 (TB) 比女性。然而，关于这一主题的研究主要集中在描述 结核病的流行病学以性别特异性的方式进行，很少甚至没有探索其驱动的生物学机制 结核病结果的性别差异。为此，2019年，我启动了一个研究项目，作为职业生涯的一部分 开发奖（K43TW011426）研究性类固醇激素的作用，即睾酮和 雌二醇，对结核病的免疫反应。在这个项目开始时，我直接受到以下影响： 不可预见的挑战，包括 COVID-19 大流行和马里的长期危机，导致无法 前往美国参加体验式培训，并从国际供应商处采购试剂和用品 常规费用。我现在提议补充活动，包括实验室培训和实验 在约翰霍普金斯大学和马里大学临床研究中心（UCRC）进行。 这些活动包括多参数流式细胞术以及免疫细胞与分枝杆菌的共同处理 抗原和性类固醇激素先通过流式细胞术离体采集。这些活动都经过精心 旨在直接响应完成家长奖中提出的实验的迫切需要， 增加明年申请 R 类申请的成功可能性。

项目成果

Sex and Gender Differences in Tuberculosis Pathogenesis and Treatment Outcomes.

结核病发病机制和治疗结果的性别差异。

• DOI: 10.1007/978-3-031-35139-6_6
• 发表时间: 2023
• 期刊: Current topics in microbiology and immunology
• 作者: Dabitao,Djeneba;Bishai,WilliamR
• 通讯作者: Bishai,WilliamR

Relationship between patient sex and anatomical sites of extrapulmonary tuberculosis in Mali.

• DOI: 10.1016/j.jctube.2023.100389
• 发表时间: 2023-12
• 期刊: JOURNAL OF CLINICAL TUBERCULOSIS AND OTHER MYCOBACTERIAL DISEASES
• 影响因子: 2
• 作者: Baya, Bocar;Sanogo, Ibrahim;Kone, Mahamadou;Soumare, Dianguina;Ouattara, Kadidia;Somboro, Amadou;Wague, Mamadou;Coulibaly, Nadie;Koloma, Isaac;Coulibaly, Mariam;Nantoume, Mohamed;Perou, Mamadou;Kone, Kadidia;Coulibaly, Djeneba;Diarra, Hawa Boukary;Kone, Bourahima;Diarra, Ayouba;Coulibaly, Mamadou D.;Sanogo, Moumine;Diarra, Bassirou;Diakite, Mahamadou;Achenbach, Chad J.;Doumbia, Seydou;Bishai, William R.;Klein, Sabra L.;Holl, Jane L.;Diallo, Souleymane;Murphy, Robert L.;Toloba, Yacouba;Dabitao, Djeneba
• 通讯作者: Dabitao, Djeneba