The role of NK cells in HIV and tuberculosis co-infection

NK 细胞在 HIV 和结核病合并感染中的作用

• 批准号: 8121984
• 负责人: Ramakrishna Vankayalapati
• 金额: $ 19.39万
• 依托单位: UNIVERSITY OF TEXAS HLTH CTR AT TYLER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-26 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8121984
• 关键词: Affect; Alveolar Macrophages; Autologous; CD8-Positive T-Lymphocytes; CD8B1 gene; Cause of Death; Cell Communication; Cell physiology; Cessation of life; Collaborations; Cytolysis; Data; Defect; Genetic; Growth; HIV; HIV Infections; Human; Immune; Immune response; Immunity; Immunosuppressive Agents; In Vitro; India; Infection; Interferons; Interleukin-10; Interleukin-12; Interleukin-15; Interleukin-18; Intervention; Measures; Mediating; Mycobacterium tuberculosis; NK Cell Activation; Natural Killer Cells; Patients; Persons; Population; Predisposition; Production; Publishing; Recombinants; Regulatory T-Lymphocyte; Research; Risk; Role; Series; Societies; System; T cell response; T-Lymphocyte; Testing; Tuberculosis; base; cytokine; improved; interleukin-22; macrophage; monocyte; mycobacterial; prevent; receptor; response; therapy development; vaccination against tuberculosis

DESCRIPTION (provided by applicant): Over the past 10 years, we have published a series of articles demonstrating that human NK cells have the potential to contribute to both innate and adaptive immune responses to M. tb. NK cells lyse M. tb-infected alveolar macrophages and produce IL-22, which inhibits intracellular growth of M. tb. NK cells also enhance T-cell responses by lysing M. tb-expanded immunosuppressive CD4+ regulatory T cells (Tregs) and by upregulating CD8+ T-cell responses in persons with LTBI. Our recent unpublished data also show NK cells contribute to T-cell responses to BCG vaccination. Since 2007, we have been collaborating with Dr. Vijaya Valluri at the Blue Peter Research Center, LEPRA Society, Hyderabad, India on studies of NK cells and Tregs. Based on our data and our established collaboration with Dr. Valluri's group, We propose the following aims. 1) Determine if NK cell responses to M. tb are reduced in HIV+ persons with LTBI. We will compare the capacity of NK cells from HIV- and HIV+ persons, with or without LTBI, to mediate innate responses to M. tb and evaluate the capacity of NK cells from HIV- and HIV+ persons, with or without LTBI, to affect T-cell responses 2) Determine if immune-based interventions can enhance NK cell and T-cell function in HIV+ persons with LTBI and active TB. We will devise interventions to improve NK cell function in HIV+ persons with LTBI, determine if interventions to improve NK cell function also enhance T-cell function in HIV+ persons with LTBI and determine if they enhance NK cell and T-cell function in HIV+ persons with active TB. PUBLIC HEALTH RELEVANCE: Mycobacterium tuberculosis infects one-third of the world's population and causes almost 2 million deaths per year. HIV infection markedly increases susceptibility to TB, and HIV-infected persons with latent tuberculosis infection (LTBI) have an 800-fold greater risk of developing active TB. The proposed studies will improve our understanding of the mechanisms that mediate susceptibility to TB in HIV+ persons, and facilitate development of interventions to improve NK cell function and prevent progression of LTBI in HIV-infected persons.

描述（由申请人提供）：在过去10年中，我们发表了一系列文章，证明人NK细胞具有促进对M的先天性和适应性免疫应答的潜力。TB. NK细胞裂解M.肺结核感染的肺泡巨噬细胞产生IL-22，IL-22抑制M. TB. NK细胞还通过溶解M增强T细胞应答。TB-扩增的免疫抑制性CD 4+调节性T细胞（T细胞）和上调LTBI患者的CD 8 + T细胞应答。我们最近未发表的数据也表明NK细胞有助于T细胞对BCG疫苗接种的反应。自2007年以来，我们一直与印度海得拉巴LEPRA协会Blue Peter研究中心的Vijaya Vadii博士合作研究NK细胞和TcB。根据我们的数据和我们与Vesli博士小组建立的合作关系，我们提出以下目标。1)确定NK细胞是否对M.结核病在HIV阳性的LTBI患者中减少。我们将比较来自HIV-和HIV+患者的NK细胞在有或没有LTBI的情况下介导对M. 2）确定基于免疫的干预是否可以增强患有LTBI和活动性TB的HIV+患者的NK细胞和T细胞功能。我们将设计干预措施来改善HIV+ LTBI患者的NK细胞功能，确定改善NK细胞功能的干预措施是否也能增强HIV+ LTBI患者的T细胞功能，并确定它们是否能增强HIV+活动性TB患者的NK细胞和T细胞功能。 公共卫生相关性：结核分枝杆菌感染了世界三分之一的人口，每年造成近200万人死亡。艾滋病毒感染显著增加了对结核病的易感性，潜伏性结核病感染（LTBI）的艾滋病毒感染者患活动性结核病的风险增加了800倍。拟议的研究将提高我们对介导HIV+人群对TB易感性的机制的理解，并促进干预措施的开发，以改善NK细胞功能并预防HIV感染者LTBI的进展。