Cytotoxic activities of CD8⁺ T cells collaborate with macrophages to protect against blood-stage murine malaria.
Cytotoxic activities of CD8⁺ T cells collaborate with macrophages to protect against blood-stage murine malaria.
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DOI：
10.7554/elife.04232
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发表时间：
2015-03-11
期刊：
影响因子：
7.7
通讯作者：
Hisaeda H
中科院分区：
文献类型：
--
作者：
Imai T;Ishida H;Suzue K;Taniguchi T;Okada H;Shimokawa C;Hisaeda H
CD 8 + T细胞对血液期疟疾提供的保护性免疫仍然存在争议，因为在寄生虫感染的人红细胞上没有显示MHC I类分子。我们最近报道了啮齿类疟原虫感染表达主要组织相容性复合体（MHC）I类抗原的成红细胞，这些抗原被CD 8 + T细胞识别。在这项研究中，我们证明，CD 8 + T细胞的细胞毒活性有助于保护小鼠对血液阶段疟疾的Fas配体（FasL）依赖的方式。感染疟原虫的成红细胞表达死亡受体Fas。CD 8 + T细胞以细胞与细胞接触依赖性方式诱导受感染的成红细胞上的磷脂酰丝氨酸（PS）的外化。PS增强吞噬细胞对感染红系细胞的吞噬。作为PS受体，T细胞免疫球蛋白结构域和粘蛋白结构域包含分子4（Tim-4）有助于疟疾寄生虫感染细胞的吞噬作用。我们的研究结果提供了深入了解的分子机制的保护性免疫所发挥的CD 8 + T细胞与吞噬细胞合作。http://dx.doi.org/10.7554/eLife.04232.001免疫系统由几种不同类型的细胞组成，它们共同作用以预防感染和疾病。例如，称为细胞毒性CD 8 + T细胞的免疫细胞杀死肿瘤细胞或其他感染的细胞。要做到这一点，CD 8 + T细胞必须识别肿瘤或感染细胞表面的某些分子并与它们结合。疟疾是一种由疟原虫引起的传染病，疟原虫通过蚊子在个体之间传播。这种寄生虫能够逃避免疫系统，以至于免疫系统如何试图阻止感染还没有得到很好的理解。这使得很难开发出一种预防疟疾的疫苗。在疟疾感染的后期，寄生虫感染宿主的红细胞。长期以来，人们认为CD 8 + T细胞无助于消除被疟原虫感染的红细胞。然而，最近在小鼠中的研究表明，CD 8 + T细胞确实对受感染的成红细胞（发育成红细胞的前体细胞）有反应，并且CD 8 + T细胞有助于保护小鼠免受血液阶段疟疾的侵害。现在，Imai等人描述了小鼠中的CD 8 + T细胞如何帮助杀死感染约氏疟原虫（一种用于研究小鼠疟疾的寄生虫）的成红细胞。受感染的细胞在其表面显示一种称为Fas的蛋白质。Imai等人发现，在疟疾感染期间，CD 8 + T细胞产生一种可以与Fas相互作用的蛋白质。这种相互作用导致受感染的细胞将信号分子移动到其外表面，这鼓励另一种类型的免疫细胞吞噬并摧毁受感染的细胞。关于CD 8 + T细胞如何对抗血液中的疟原虫寄生虫的知识现在可以帮助开发新型的疟疾血液阶段疫苗。DOI：http://dx.doi.org/10.7554/eLife.04232.002网站
The protective immunity afforded by CD8+ T cells against blood-stage malaria remains controversial because no MHC class I molecules are displayed on parasite-infected human erythrocytes. We recently reported that rodent malaria parasites infect erythroblasts that express major histocompatibility complex (MHC) class I antigens, which are recognized by CD8+ T cells. In this study, we demonstrate that the cytotoxic activity of CD8+ T cells contributes to the protection of mice against blood-stage malaria in a Fas ligand (FasL)-dependent manner. Erythroblasts infected with malarial parasites express the death receptor Fas. CD8+ T cells induce the externalization of phosphatidylserine (PS) on the infected erythroblasts in a cell-to-cell contact-dependent manner. PS enhances the engulfment of the infected erythroid cells by phagocytes. As a PS receptor, T-cell immunoglobulin-domain and mucin-domain-containing molecule 4 (Tim-4) contributes to the phagocytosis of malaria-parasite-infected cells. Our findings provide insight into the molecular mechanisms underlying the protective immunity exerted by CD8+ T cells in collaboration with phagocytes. DOI: http://dx.doi.org/10.7554/eLife.04232.001 The immune system consists of several different types of cell that work together to prevent infection and disease. For example, immune cells called cytotoxic CD8+ T cells kill tumor cells or other cells that are infected. To do so, the CD8+ T cells must recognize certain molecules on the surface of the tumor or infected cells and bind to them. Malaria is an infectious disease caused by the Plasmodium parasite, which is transferred between individuals by mosquitoes. The parasite is able to evade the immune system—so much so that it is not well understood how the immune system tries to respond to stop the infection. This has made it difficult to develop a vaccine that protects against malaria. During the latter stages of a malaria infection, the parasite infects the host's red blood cells. It was long believed that CD8+ T cells did not help to eliminate the red blood cells that had been infected by Plasmodium. However, recent work in mice suggested that CD8+ T cells do respond to infected erythroblasts—precursor cells that develop into red blood cells—and that CD8+ T cells help protect mice against blood-stage malaria. Now, Imai et al. describe how the CD8+ T cells in mice help to kill erythroblasts infected with Plasmodium yoelli, a species of the parasite used to study malaria in mice. The infected cells display a protein called Fas on their surface. Imai et al. found that, during a malaria infection, the CD8+ T cells produce a protein that can interact with Fas. This interaction causes the infected cell to move a signaling molecule to its outside surface, which encourages another type of immune cell to engulf and destroy the infected cell. This knowledge of how CD8+ T cells fight Plasmodium parasites in the bloodstream could now help to develop new types of blood-stage vaccine for malaria. DOI: http://dx.doi.org/10.7554/eLife.04232.002
影响因子：
3.7
作者：
Morello A;Daburon S;Castroviejo M;Moreau JF;Dechanet-Merville J;Taupin JL
通讯作者：
Taupin JL