EXPRESSION OF HEAT SHOCK PROTEIN WHICH CONTROLS THE INFECTIVITY OF TOXOPLASMA AND HOST RESISTANCE AGAINST INFECTION

控制弓形虫感染性和宿主对感染的抵抗力的热休克蛋白的表达

• 批准号: 07670277
• 负责人: NAGASAWA Hideyuki
• 金额: $ 1.41万
• 依托单位: OBIHIRO UNIVERSITY OF AGRICULTURE AND VETERINARY MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670277/
• 关键词: Heat Shock Potein; HSP65; Toxoplasma gondii; gammadelta T cells; Protective immunity; SCID mouse

Characterization of effector and regulatory functions of HSPs in other hosts and microbial systems should provide insight into mechanisms of virulence and protective adaptations that control virulence. Thus, it seems likely that HSPs could assume a critical importance in numerous host-parasite relationships, including resistance of host to otherwise destructively virulent parasites. At any rate, it seems clear from a series of our experiments that expression of HSP65 on peritoneal macrophages correlates dramatically with capacity to inhibit destructivc consequences of infection with both low-virulence and high-virulence strains of T.gondii.From these bases, the expression mechanism and the biological role of HSP65 may be as follows. As first step after infection with a low-virulence of Toxoplasma, circulating gammadelta T cells recognize either Toxoplasma-derived HSP65 or host-derived HSP65, and then they accumulate and activated. At the second step, macrophages activated by gammadelta … More T cells probably via certain cytokine pathways exhibit enhanced respiratory burst releasing noxious molecules, e.g.oxygen metabolites, a major protective mechanism against intracellular pathogens like T.gondii. As the third stcp, activated macrophages synthesize endogenous HSP65 for protection against these toxic molecules, for repairment of damaged functions of themselves or for effective antigen-presentation. Finaly, either gammadelta T cells and alphabeta T cells reactive to HSP65 or alphabeta T cells specific for Toxoplasma antigen further accumulate and are activated. Such T cells directly destroy the host macrophages or activate macrophages to kill the intracellular Toxoplasma parasites.We showed here that gammadelta T cells rather than alphabeta T cells participate in the induction of HSP65 on macrophages of hosts which have acquired resistance against toxoplasmosis. However, it stili remains undetermined about the mechanisms of expression of HSP65 and the role of this protein in the protection against this infection. Furthermore, it is very important to elucidate whether gammadelta T cells which induce the expression of HSP65 and those which accumulate recognizing HSP65 involve in the same functional subset, and whether the former and the latter subset (s) of gammadelta T cells recognize different antigens each other or the same epitope of HSP65. Moreover, it is of interest to investigate the relationship between gammadelta T cells and alphabeta T cells in protective immunity, both of which have an ability to induce this protein. Less

表征热休克蛋白在其他宿主和微生物系统中的效应和调节功能，将有助于深入了解毒力机制和控制毒力的保护性适应。因此，热休克蛋白可能在许多宿主-寄生虫关系中起着至关重要的作用，包括宿主对其他破坏性毒性寄生虫的抗性。无论如何，我们的一系列实验似乎清楚地表明，HSP65在腹膜巨噬细胞上的表达与抑制低毒力和高毒力弓形虫菌株感染的破坏性后果的能力显著相关。从这些基础来看，HSP65的表达机制和生物学作用可能如下。作为感染低毒力弓形虫后的第一步，循环γ - δ T细胞识别弓形虫源性HSP65或宿主源性HSP65，然后它们积累并激活。更多的T细胞可能通过某些细胞因子通路表现出增强的呼吸爆发，释放有害分子，例如氧代谢物，这是对抗细胞内病原体（如弓形虫）的主要保护机制。作为第三步，活化的巨噬细胞合成内源性HSP65，以保护自身免受这些有毒分子的侵害，修复自身受损的功能，或进行有效的抗原呈递。最后，对HSP65反应的γ - T细胞和α - T细胞或对弓形虫抗原特异性的α - T细胞进一步积累并被激活。这种T细胞直接破坏宿主巨噬细胞或激活巨噬细胞杀死细胞内的弓形虫寄生虫。我们在这里表明，γ - T细胞而不是α - T细胞参与了对弓形虫病获得抗性的宿主巨噬细胞的HSP65诱导。然而，HSP65的表达机制以及该蛋白在抗感染中的作用尚不清楚。此外，阐明诱导HSP65表达的γ δ T细胞和积累识别HSP65的γ δ T细胞是否在同一个功能亚群中，以及γ δ T细胞的前者和后者亚群是否相互识别不同的抗原或识别相同的HSP65表位是非常重要的。此外，研究γ - T细胞和α - T细胞在保护性免疫中的关系也很有意义，它们都有能力诱导这种蛋白。少

项目成果

Hisaeda, H., Sakai, T., Nagasawa, H., Ishikawa, H., Yasutomo, K., Maekawa, Y.and Himeno, K.: "Contribution of extrathymic gammadelta T cells to the expression of heat-shock protein and to protective immunity in mice infected with Toxoplasma gondii." Immun

Hisaeda, H.、Sakai, T.、Nagasawa, H.、Ishikawa, H.、Yasutomo, K.、Maekawa, Y. 和 Himeno, K.：“胸腺外 γδ T 细胞对热休克蛋白表达的贡献

Nagasawa,H.et al: "Role of Heat Shock Proteins in Protective Immunity against Infection with Toxoplasma gondii." Bull. Soc. Fr-Jpn. Vet.6(2). 154-162 (1995)

Nagasawa,H.et al：“热休克蛋白在抵抗弓形虫感染的保护性免疫中的作用。”

Hisaeda,H.et al: "Contribution of extrathymic γδ T cells to the expression of heat-shock protein and to protective immunity in mice infected with Toxoplasma gondii." Immunology. 88. 551-557 (1996)

Hisaeda, H. 等人：“胸腺外 γδ T 细胞对弓形虫感染小鼠的热休克蛋白表达和保护性免疫的贡献。” 88. 551-557 (1996)。

Hisaeda, H.et al.: "γδ T cells play an important roles in expression of HSP65 and in acquiring protective immune response against infection with Toxoplasma gondii." J.Immunol. 154. 244-251 (1995)

Hisaeda, H. 等人：“γδ T 细胞在 HSP65 的表达和获得针对弓形虫感染的保护性免疫反应中发挥着重要作用。J.Immunol。”

Furukawa, A.et al.: "Establishment of xeno-chimera without GVHD in NK cell-depleted SCID mice by grafting rat fetal liver cells." Cellular Immunol.164. 176-181 (1995)

Furukawa, A.等人：“通过移植大鼠胎儿肝细胞，在 NK 细胞耗尽的 SCID 小鼠中建立无 GVHD 的异种嵌合体。”