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
- 来源:
- 关键词:Acquired Immunodeficiency SyndromeAddressAffectAnti-Inflammatory AgentsBrainBrain InjuriesCD4 Positive T LymphocytesCell secretionCellsCellular ImmunityCerebrospinal FluidCessation of lifeClinicalClinical DataComaCryptococcosisCryptococcusCryptococcus neoformansCryptococcus neoformans infectionDiseaseEncephalitisEquilibriumFOXP3 geneGenesGenetic PolymorphismGrowthHIVHIV SeronegativityHIV SeropositivityHIV/AIDSHumanImmuneImmune responseImmunityImmunocompromised HostImpairmentIndividualInfectionInflammationInflammatoryInflammatory ResponseInhalationInterleukin-10LifeLungMaintenanceMediatingMeningoencephalitisMicrobeMolecularMusMycosesOutcomePatientsPersonsPlayPredispositionProductionProliferatingPropertyRegulationRegulatory T-LymphocyteRoleSeveritiesSignal TransductionSourceSyndromeTestingTherapeuticantiretroviral therapyblood-brain barrier crossingbrain sizecytokinefungusimmune reconstitutionimmunopathologyimmunoregulationimprovedinterleukin-10 receptormRNA Expressionmigrationmortalitymouse modelpathogenpathogenic funguspreventreceptorresponsetherapeutic development
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
期刊论文数量(0)
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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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