Mechanisms of balancing the immune response during cryptococcal meningoencephalitis

隐球菌性脑膜脑炎期间平衡免疫反应的机制

基本信息

  • 批准号:
    10761918
  • 负责人:
  • 金额:
    $ 19.23万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-07-01 至 2025-06-30
  • 项目状态:
    未结题

项目摘要

Project Summary Cryptococcosis is an opportunistic fungal infection that is caused by Cryptococcus neoformans and often occurs in immunocompromised individuals including HIV/AIDS patients. Although the infection starts in the lung via inhalation of the pathogenic fungus, the most common manifestation of cryptococcosis is meningoencephalitis, which is a leading cause of mortality of HIV/AIDS patients and accounts for proximately 181,000 deaths worldwide annually. The high susceptibility of HIV/AIDS patients to C. neoformans infection is attributed to their impaired cellular immunity. Consequently, C. neoformans proliferates in the brain without control, leading to microbe-mediated brain damage. Antiretroviral therapy (ART) is a major advance in treating HIV/AIDS patients by restoring cellular immune responses. However, after initiation of ART, up to 30% of HIV/AIDS patients with cryptococcosis develop immune reconstitution inflammatory syndrome (IRIS), an aberrant excessive immune response leading to host-mediated brain damage. Furthermore, post-infectious inflammatory response syndrome (PIIRS) occurs frequently in HIV-negative patients with cryptococcal meningoencephalitis. Therefore, a robust immune response is required for controlling the fungal growth; however, the immune response must be tightly controlled to avoid host-mediated brain damage during cryptococcal meningoencephalitis. A critical gap in our understanding remains: what are the mechanisms of maintaining the balance between protective immune responses and immunopathology during cryptococcal meningoencephalitis-associated IRIS? IL-10 is an important cytokine with anti-inflammatory properties and its production was enhanced in the cerebrospinal fluid of HIV/AIDS patients during cryptococcal IRIS. Based on clinical data and our preliminary murine studies, we hypothesize that IL-10 is critically involved in balancing the immune responses during cryptococcal meningoencephalitis-associated IRIS. We will test the hypothesis in a murine model that closely mimics cryptococcal IRIS of HIV/AIDS patients, by addressing the following aims: (1) To determine the mechanism(s) involved in regulation of the immune responses by IL-10 during cryptococcal meningoencephalitis-associated IRIS; (2) To determine the mechanism(s) involved in induction of IL-10 in the brain during cryptococcal meningoencephalitis-associated IRIS. If successful, the findings from this study would be fundamental for understanding regulation of immune balance during cryptococcal meningoencephalitis-associated IRIS and provide scientific basis for targeting this cytokine aiming at controlling deleterious inflammation in the brain of cryptococcal IRIS/AIDS patients.
项目总结

项目成果

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Meiqing Shi其他文献

Meiqing Shi的其他文献

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{{ truncateString('Meiqing Shi', 18)}}的其他基金

Interactions of Cryptococcus neoformans with mononuclear phagocytes in the brain
新型隐球菌与大脑中单核吞噬细胞的相互作用
  • 批准号:
    10667732
  • 财政年份:
    2023
  • 资助金额:
    $ 19.23万
  • 项目类别:
Filtering of disseminating Cryptococcus neoformans out of vasculature
将传播的新型隐球菌从脉管系统中过滤出来
  • 批准号:
    9387721
  • 财政年份:
    2017
  • 资助金额:
    $ 19.23万
  • 项目类别:
In vivo mechanisms of brain invasion by Cryptococcus neoformans
新型隐球菌脑侵袭的体内机制
  • 批准号:
    9912711
  • 财政年份:
    2017
  • 资助金额:
    $ 19.23万
  • 项目类别:
Brain dissemination of Cryptococcus neoformans mediated by neutrophils
中性粒细胞介导的新型隐球菌的脑传播
  • 批准号:
    8808266
  • 财政年份:
    2014
  • 资助金额:
    $ 19.23万
  • 项目类别:

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