Innate immune functions of microglia isolated from human glioma patients.
Innate immune functions of microglia isolated from human glioma patients.
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DOI：
10.1186/1479-5876-4-15
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发表时间：
2006-03-30
影响因子：
7.4
通讯作者：
Heimberger AB
中科院分区：
文献类型：
--
作者：
Hussain SF;Yang D;Suki D;Grimm E;Heimberger AB
先天免疫被认为是宿主防御的第一道防线，小胶质细胞可能在介导针对人脑创伤和感染挑战的有效先天免疫反应中发挥着关键作用。神经胶质瘤患者适应性免疫系统的基本损伤已得到研究；然而，目前尚不清楚小胶质细胞是否能够在人类胶质瘤患者的免疫抑制肿瘤微环境中产生先天免疫和随后的适应性抗肿瘤免疫反应。因此，我们对新鲜分离的人神经胶质瘤浸润性小胶质细胞（GIM）的先天免疫表型和功能进行了新的表征。手术切除后立即通过连续 Percoll 纯化从患者肿瘤中分离出 GIM。使用流式细胞术、吞噬作用和肿瘤细胞毒性测定来分析这些细胞的表型和功能。 GIM 表达显着水平的 Toll 样受体 (TLR)，但它们不分泌任何对于形成有效的先天免疫反应至关重要的细胞因子（IL-1β、IL-6、TNF-α）。与先天巨噬细胞功能类似，GIM 可以介导吞噬作用和非 MHC 限制的细胞毒性。然而，与从正常大脑中分离的小胶质细胞相比，它们介导肿瘤细胞毒性的能力在统计学上较差。此外，Fas配体（FasL）的表达低至缺失，表明传入淋巴细胞群的凋亡可能不是小胶质细胞免疫抑制的主要模式。我们首次证明，尽管人类神经胶质瘤处于免疫抑制环境中，GIM 仍能够产生吞噬作用、细胞毒性和 TLR 表达等先天免疫反应，但尚不具备分泌关键细胞因子的能力。进一步了解这些先天免疫功能可能在了解和开发针对人类恶性胶质瘤的有效免疫疗法方面发挥关键作用。
Innate immunity is considered the first line of host defense and microglia presumably play a critical role in mediating potent innate immune responses to traumatic and infectious challenges in the human brain. Fundamental impairments of the adaptive immune system in glioma patients have been investigated; however, it is unknown whether microglia are capable of innate immunity and subsequent adaptive anti-tumor immune responses within the immunosuppressive tumor micro-environment of human glioma patients. We therefore undertook a novel characterization of the innate immune phenotype and function of freshly isolated human glioma-infiltrating microglia (GIM). GIM were isolated by sequential Percoll purification from patient tumors immediately after surgical resection. Flow cytometry, phagocytosis and tumor cytotoxicity assays were used to analyze the phenotype and function of these cells. GIM expressed significant levels of Toll-like receptors (TLRs), however they do not secrete any of the cytokines (IL-1β, IL-6, TNF-α) critical in developing effective innate immune responses. Similar to innate macrophage functions, GIM can mediate phagocytosis and non-MHC restricted cytotoxicity. However, they were statistically less able to mediate tumor cytotoxicity compared to microglia isolated from normal brain. In addition, the expression of Fas ligand (FasL) was low to absent, indicating that apoptosis of the incoming lymphocyte population may not be a predominant mode of immunosuppression by microglia. We show for the first time that despite the immunosuppressive environment of human gliomas, GIM are capable of innate immune responses such as phagocytosis, cytotoxicity and TLR expression but yet are not competent in secreting key cytokines. Further understanding of these innate immune functions could play a critical role in understanding and developing effective immunotherapies to malignant human gliomas.
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影响因子：
4.4
作者：
Chen, YL;Chen, SH;Yang, BC
通讯作者：
Yang, BC
影响因子：
15.9
作者：
Kreutzberg, GW
通讯作者：
Kreutzberg, GW
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通讯作者：
Kolb, H
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通讯作者：
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通讯作者：
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