Immune responses to Pneumocystis colonization and infection in a simian model of AIDS.
Immune responses to Pneumocystis colonization and infection in a simian model of AIDS.
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艾滋病猿模型中肺孢子菌定植和感染的免疫反应。
DOI：
10.1111/j.1550-7408.2003.tb00675.x
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Norris,KarenA
中科院分区：
文献类型：
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作者：
Patil,SangitaP;Board,KathyrnF;Lebedeva,IrinaP;Norris,KarenA
肺孢子菌肺炎 (PcP) 是 HIV 感染者以及其他免疫功能低下患者发病和死亡的主要原因。急性 PcP 的特点是肺部淋巴细胞（主要是 CD8+ T 细胞）以及中性粒细胞浸润。此外，肺部促炎细胞因子 INF-γ、TNF-α 和 IL-8 的水平也会增加。这些炎症细胞及其分泌的细胞因子在 PcP 的控制或发病机制中的作用尚不清楚。本研究的目的是评估感染过程中猕猴肺部发生的艾滋病模型中对肺孢子虫的免疫反应的进展。感染猿猴免疫缺陷病毒（SIV）的恒河猴经支气管内感染源自猕猴的肺孢子虫。每两周进行一次支气管肺泡灌洗，并分析细胞和细胞因子组成以及肺孢子虫和 SIV 感染的进展。该模型中的肺孢子虫感染导致了延长的无症状定植期，其特征是产生 INF-γ 的 CD8+ T 细胞早期流入肺部，并在整个感染过程中持续存在。在观察到呼吸道症状之前，中性粒细胞浸润以及 TNF-α 和 IL-8 水平升高也持续数周至数月。由于该病程与 AIDS 中的 PcP 病程非常相似，因此肺孢子虫-SIV 模型将有助于解决肺部长期暴露于炎症介质的临床后果。
Pneumocystis pneumonia (PcP) is a leading cause of morbidity and mortality in HIV–infected individuals, as well as in other immunocompromised patients. Acute PcP is characterized by infiltration of the lungs by lymphocytes, primarily CD8+ T cells, as well as neutrophils. In addition, there is an increase in the levels of the proinflammatory cytokines INF-γ, TNF-α and IL-8 in the lungs. The role of these inflammatory cells and their secreted cytokines in control or pathogenesis of PcP is not well understood. The aim of this study was to evaluate the progression of immune responses to Pneumocystis in a model of AIDS occurring in the lungs of macaques during the course of infection. Simian immunodeficiency virus (SIV)-infected rhesus macaques were intrabronchially infected with macaque-derived Pneumocystis. Bronchoalveolar lavage was performed biweekly and analysed for cellular and cytokine composition and for the progression of Pneumocystis and SIV infection. Pneumocystis infection in this model resulted in a protracted, asymptomatic colonization period, characterized by an early influx of INF-γ producing CD8+ T cells in the lungs that persisted throughout the infection. Neutrophil infiltration and increased levels of TNF-α and IL-8 also persisted weeks to months before respiratory symptoms were observed. As the disease course closely resembles that of PcP in AIDS, the Pneumocystis-SIV model will be useful in addressing the clinical consequences of prolonged exposure of the lungs to inflammatory mediators.