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首页> 外文期刊>Infection and immunity >Cytokine and Inducible Nitric Oxide Synthase mRNA Expression during Experimental Murine Cryptococcal Meningoencephalitis
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Cytokine and Inducible Nitric Oxide Synthase mRNA Expression during Experimental Murine Cryptococcal Meningoencephalitis

机译：实验性小鼠隐球菌性脑膜脑炎期间细胞因子和诱导型一氧化氮合酶mRNA表达

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The immune events that take place in the central nervous system (CNS) during cryptococcal infection are incompletely understood. We used competitive reverse transcription-PCR to delineate the time course of the local expression of mRNAs encoding a variety of cytokines and inducible nitric oxide synthase (iNOS) during progressive murine cryptococcal meningoencephalitis and assessed the CNS inflammatory response using immunohistochemistry. Interleukin 18 (IL-18), transforming growth factor β1, and IL-12p40 mRNAs were constitutively expressed in the brains of infected and uninfected mice; IL-2 mRNA was not detected at any time. Increased levels of transcripts corresponding to IL-1α, tumor necrosis factor alpha (TNF-α), and iNOS were detected as early as day 1 postinfection, with TNF-α rising by ～30-fold and iNOS increasing by ～5-fold by day 7. Each remained at these levels thereafter. IL-4, IL-6, and gamma interferon transcripts were detected on day 5, and IL-1β and IL-10 transcripts were detected beginning on day 7. Once detected, each remained at a relatively constant level through 28 days of infection. This cytokine profile does not suggest a polarized Th1 or Th2 response. Immunohistochemistry did not reveal inflammatory infiltrates before day 7, despite the presence of cryptococci. Intraparenchymal abscesses with inflammatory cells in their peripheries were found beginning on day 10. The infiltrates were comprised primarily of cells expressing CD4, CD8, or CD11b; low numbers of cells expressing CD45R/B220 were also present. The persistence of Cryptococcus observed in the CNS may result from an ineffective immune response, perhaps owing to an insufficient anticryptococcal effector function of endogenous glial cells resulting from competing pro- and anti-inflammatory cytokines. These data detail the immune response in the brain and could be important for the future design of specific immunomodulatory therapies for this important opportunistic infection.
机译：隐球菌感染期间在中枢神经系统（CNS）中发生的免疫事件尚未完全了解。我们使用竞争性逆转录-PCR来描述进行性鼠隐球菌性脑膜脑炎期间编码多种细胞因子和诱导型一氧化氮合酶（iNOS）的mRNA局部表达的时程，并使用免疫组织化学评估中枢神经系统的炎症反应。白细胞介素18（IL-18），转化生长因子β1和IL-12p 40 mRNA在感染和未感染小鼠的大脑中组成性表达。任何时候都未检测到IL-2 mRNA。最早在感染后第1天就检测到与IL-1α，肿瘤坏死因子α（TNF-α）和iNOS相对应的转录本水平升高，其中TNF-α升高约30倍，而iNOS升高约5倍。第7天。此后每个都保持在这些水平。在第5天检测到IL-4，IL-6和γ干扰素转录物，并从第7天开始检测到IL-1β和IL-10转录物。一旦检测到，它们在感染28天后始终保持相对稳定的水平。这种细胞因子谱并不表明极化的Th1或Th2反应。尽管存在隐球菌，但免疫组织化学在第7天之前并未显示炎性浸润。从第10天开始发现周围有炎性细胞的实质内脓肿。浸润主要由表达CD4，CD8或CD11b的细胞组成。还存在少量表达CD45R / B220的细胞。在中枢神经系统中观察到的隐球菌的持续存在可能是由于无效的免疫反应所致，这可能是由于内源性神经胶质细胞的抗隐球菌效应功能不足所致，这些内源性神经胶质细胞是由促炎和消炎性细胞因子竞争引起的。这些数据详细说明了大脑中的免疫反应，对于这种重要的机会性感染的特异性免疫调节疗法的未来设计可能非常重要。

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