How HIV-1 inhibits phagocytosis by macrophages

HIV-1如何抑制巨噬细胞的吞噬作用

• 批准号: nhmrc : 281214
• 负责人: A/Pr Anthony Jaworowski
• 金额: $ 10.7万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2004
• 资助国家: 澳大利亚
• 起止时间: 2004-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/hiv-1-inhibits-phagocytosis-macrophages/76783
• 关键词: How; HIV; inhibits; phagocytosis; macrophages

Last year an estimated 3.1 million people died of AIDS (source: UNAIDS, Dec 2002) equivalent to the number killed by tuberculosis and malaria combined. AIDS-related opportunistic infections (OIs) are the main cause of death for AIDS patients, especially in resource constrained countries where access to antiretroviral and antibiotic therapy is limited. Attempts to limit the epidemic have failed and new foci have emerged in Eastern Europe, Central Asia and, of particular relevance for us, South East Asia, underlining the fact that safe and effective treatment for AIDS-related OIs will be a global health priority for the foreseeable future. People with healthy immune systems do not get OIs since the germs that cause such infections are efficiently ingested and subsequently destroyed by cells called macrophages. We have discovered that the virus that causes AIDS, HIV-1, interferes with the ability of macrophages to ingest opportunistic pathogens by the 2 most important mechanisms used for this purpose. We believe that this is the direct cause for the susceptibility of AIDS patients to many of the opportunistic pathogens that cause their OIs. The purpose of this grant will be to understand the biochemical basis underlying these 2 defects in macrophage function. This will help in the design of safe, adjunctive therapies aimed at improving macrophage function and reducing the risk of HIV-infected individuals developing AIDS-related OIs.

去年，估计有310万人死于艾滋病（资料来源：联合国艾滋病规划署，2002年12月），相当于死于肺结核和疟疾的人数之和。与艾滋病有关的机会性感染是艾滋病患者死亡的主要原因，特别是在资源有限的国家，抗逆转录病毒和抗生素治疗有限。限制这一流行病的努力已经失败，在东欧、中亚以及与我们特别相关的东南亚出现了新的疫源地，这突出表明，在可预见的未来，安全和有效地治疗与艾滋病有关的感染性疾病将是全球卫生的优先事项。免疫系统健康的人不会感染OIs，因为引起这种感染的细菌被有效地摄入，随后被称为巨噬细胞的细胞破坏。我们已经发现，导致艾滋病的病毒HIV-1通过两种最重要的机制干扰巨噬细胞摄取机会性病原体的能力。我们认为这是艾滋病患者对许多导致其OI的机会性病原体易感的直接原因。这项资助的目的是了解巨噬细胞功能中这两种缺陷的生化基础。这将有助于设计安全、有效的治疗方法，旨在改善巨噬细胞功能，降低HIV感染者发生AIDS相关OI的风险。