Resistance to malaria by enhanced phagocytosis of erythrocytes in LMP7-deficient mice.
Resistance to malaria by enhanced phagocytosis of erythrocytes in LMP7-deficient mice.
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DOI：
10.1371/journal.pone.0059633
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hisaeda H
中科院分区：
文献类型：
--
作者：
Duan X;Imai T;Chou B;Tu L;Himeno K;Suzue K;Hirai M;Taniguchi T;Okada H;Shimokawa C;Hisaeda H
蛋白酶体的一般细胞功能通过蛋白质降解发生，而免疫蛋白酶体的特异性功能是优化与MHC I类相关的抗原加工。我们和其他人先前报道了免疫蛋白酶体亚单位的缺陷损害了抗原特异性CD8+ T细胞的活化，导致对肿瘤和感染的更高易感性。我们证明了CD8+ T细胞有助于保护免受疟疾寄生虫的侵害。在这项研究中，我们评估了免疫蛋白酶体在啮齿类疟原虫感染过程中的作用。出乎意料的是，与对照小鼠相比，缺乏LMP7（免疫蛋白酶体的催化亚基）的约氏疟原虫感染小鼠在感染早期显示出较低的寄生虫生长和较低的致死率。LMP7缺陷型小鼠的保护性特征与增强的免疫应答无关，因为突变型小鼠显示出相当或减弱的先天性和获得性免疫激活。红细胞免疫反应无明显差异。与野生型小鼠相比，从LMP7缺陷型小鼠纯化的寄生红细胞（pRBC）更容易被巨噬细胞吞噬。pRBC对吞噬作用的敏感性似乎与仅在感染后观察到的膜结构的畸形相关。我们的研究结果表明，LMP7缺陷小鼠的红细胞更容易变形，以应对疟疾寄生虫感染，可能导致更高的易感性吞噬和疟疾的部分抗性。
General cellular functions of proteasomes occur through protein degradation, whereas the specific function of immunoproteasomes is the optimization of antigen processing associated with MHC class I. We and others previously reported that deficiency in subunits of immunoproteasomes impaired the activation of antigen-specific CD8+ T cells, resulting in higher susceptibility to tumor and infections. We demonstrated that CD8+ T cells contributed to protection against malaria parasites. In this study, we evaluated the role of immunoproteasomes in the course of infection with rodent malaria parasites. Unexpectedly, Plasmodium yoelii infection of mice deficient in LMP7, a catalytic subunit of immunoproteasomes, showed lower parasite growth in the early phase of infection and lower lethality compared with control mice. The protective characteristics of LMP7-deficient mice were not associated with enhanced immune responses, as the mutant mice showed comparable or diminished activation of innate and acquired immunity. The remarkable difference was observed in erythrocytes instead of immune responses. Parasitized red blood cells (pRBCs) purified from LMP7-deficient mice were more susceptible to phagocytosis by macrophages compared with those from wild-type mice. The susceptibility of pRBC to phagocytosis appeared to correlate with deformity of the membrane structures that were only observed after infection. Our results suggest that RBCs of LMP7-deficient mice were more likely to deform in response to infection with malaria parasites, presumably resulting in higher susceptibility to phagocytosis and in the partial resistance to malaria.
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影响因子：
64.8
作者：
DRISCOLL, J;BROWN, MG;MONACO, JJ
通讯作者：
MONACO, JJ
影响因子：
4.4
作者：
Belnoue, E;Kayibanda, M;Rénia, L
通讯作者：
Rénia, L
影响因子：
11.4
作者：
FRUH, K;GOSSEN, M;YANG, Y
通讯作者：
YANG, Y
DOI：
10.1084/jem.187.1.97
发表时间：
1998-01-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Griffin TA;Nandi D;Cruz M;Fehling HJ;Kaer LV;Monaco JJ;Colbert RA
通讯作者：
Colbert RA
影响因子：
3.5
作者：
AKIYAMA, K;KAGAWA, S;ICHIHARA, A
通讯作者：
ICHIHARA, A