Tamura Takahiko, Kimura Kazumi, Yui Katsuyuki, Yoshida Shigeto
Division of Immunology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4, Sakamoto, Nagasaki 852-8523, Japan; Global COE Program, Nagasaki University, 1-12-4, Sakamoto, Nagasaki 852-8523, Japan; Laboratory of Vaccinology and Applied Immunology, Kanazawa University, School of Pharmacy, Kakuma-machi, Kanazawa 920-1192, Japan.
Division of Immunology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4, Sakamoto, Nagasaki 852-8523, Japan.
Exp Parasitol. 2015 Dec;159:127-35. doi: 10.1016/j.exppara.2015.09.010. Epub 2015 Sep 28.
Dendritic cells (DCs) play critical roles in innate and adaptive immunity and in pathogenesis during the blood stage of malaria infection. The mechanisms underlying DC homeostasis during malaria infection are not well understood. In this study, the numbers of conventional DCs (cDCs) and plasmacytoid DCs (pDCs) in the spleens after lethal rodent malaria infection were examined, and were found to be significantly reduced. Concomitant with up-regulation of maturation-associated molecules, activation of caspase-3 was significantly increased, suggesting induction of cell death. Studies using neutralizing antibody and gene-deficient mice showed that type I and II interferons were critically involved in activation induced cell death of cDCs during malaria infection. These results demonstrate that DCs rapidly disappeared following IFN-mediated DC activation, and that homeostasis of DCs was significantly impaired during malaria infection.
树突状细胞（DCs）在先天性和适应性免疫以及疟疾感染血液阶段的发病机制中发挥着关键作用。疟疾感染期间DC内稳态的潜在机制尚不清楚。在本研究中，检测了致死性啮齿动物疟疾感染后脾脏中常规DC（cDCs）和浆细胞样DC（pDCs）的数量，发现其显著减少。伴随着成熟相关分子的上调，半胱天冬酶-3的激活显著增加，提示细胞死亡的诱导。使用中和抗体和基因缺陷小鼠的研究表明，I型和II型干扰素在疟疾感染期间cDCs的激活诱导细胞死亡中起关键作用。这些结果表明，DCs在干扰素介导的DC激活后迅速消失，并且在疟疾感染期间DCs的内稳态显著受损。
