1. Resistance to Malaria by Enhanced Phagocytosis of Erythrocytes in LMP7-deficient Mice.
- Author
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Duan, Xuefeng, Imai, Takashi, Chou, Bin, Tu, Liping, Himeno, Kunisuke, Suzue, Kazutomo, Hirai, Makoto, Taniguchi, Tomoyo, Okada, Hiroko, Shimokawa, Chikako, and Hisaeda, Hajime
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MALARIA ,PHAGOCYTOSIS ,ERYTHROCYTES ,PEPTIDASE ,ENZYME deficiency ,PROTEASOMES ,MAJOR histocompatibility complex ,LABORATORY mice - Abstract
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. [ABSTRACT FROM AUTHOR]- Published
- 2013
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