Effects of helminth-driven immunomodulation on concurrently infected parasites and tumor cells in mice

蠕虫驱动的免疫调节对小鼠体内同时感染的寄生虫和肿瘤细胞的影响

• 批准号: 08457082
• 负责人: OHTA Nobuo
• 金额: $ 4.61万
• 依托单位: NAGOYA CITY UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457082/
• 关键词: Schistosomiasis; Plasmodium chabaudi; Strongyloides venezuelensis; cytokine; Nitric oxide; Th1; Th2; host-parasite interaction; tumor rejection; Schistosoma mansoni; UV♀1; 宿主・寄生虫相互作用; Schistosoma japonicum; Plasmodium chaboudi; 感染感受性; 虫卵肉芽腫

This study was conducted to uncover effects of helminth-driven immunomodulation on concurrent infections of other unrelated parasites in mice. Murine hosts infected with Schistosoma mansoni are thought to be in Th2-dominant situation, which might have detectable effects for the bio-defence system. Results in this study suggest that schistosome-driven Th2 response induced strong protective immunity against Strongyloides venezuelensis infection. On the other hand, S.mansoni infection did not have any detectable effects on Leishmania major infection for which Th1 response is hightly protective in particular mice strains. C57BL/6 mice are resistant against L.major through induction of Th1-dominant response, however, these mice were still resistant even in concomitant infection of S.mansoni. Schistosome-driven Th2 response seemed to impair killer T cell response in mice implanted with UV*1 fibrosarcoma cells. Unexpected results were observed in case of Plasmodium chabaudi infection in A/J mice, which is highly susceptible to P.chabaudi infection. When A/J mice were infected with S.mansoni, parasitemia was significantly suppressed, and moreover, no mice died of malaria, while all A/J mice infected with P.chabaudi alone died within 7 days. Together with these results, we conclude that schistosome infection could have deep effects on the bio-defence system of infected hosts, although the effects are highly heterogenous. Such effects are determined not only by host-schistosome interaction, but also by parasite-parasite interaction. The complicated mechanisms for determining the bio-defence system in infected hosts are involved in disease susceptibility of host population, and eradication of particular parasites might provide unexpected risk of another infective disease.

这项研究的目的是揭示蠕虫驱动的免疫调节对小鼠体内其他不相关寄生虫并发感染的影响。感染曼氏血吸虫的小鼠宿主被认为处于 Th2 主导状态，这可能对生物防御系统产生可检测到的影响。本研究结果表明，血吸虫驱动的 Th2 反应可诱导针对委内瑞拉类圆线虫感染的强大保护性免疫。另一方面，曼氏沙门氏菌感染对利什曼原虫重度感染没有任何可检测到的影响，对于利什曼原虫重度感染，Th1 反应在特定小鼠品系中具有高度保护性。 C57BL/6 小鼠通过诱导 Th1 主导反应而对 L.major 产生耐药性，然而，即使同时感染曼氏沙门氏菌，这些小鼠仍然具有耐药性。血吸虫驱动的 Th2 反应似乎会损害植入 UV*1 纤维肉瘤细胞的小鼠的杀伤性 T 细胞反应。在 A/J 小鼠感染恰鲍迪疟原虫的情况下观察到了意想不到的结果，这种小鼠对恰鲍迪疟原虫感染高度敏感。当A/J小鼠感染曼氏疟原虫后，寄生虫血症被显着抑制，而且没有小鼠死于疟疾，而仅感染查鲍迪疟原虫的所有A/J小鼠均在7天内死亡。结合这些结果，我们得出结论，血吸虫感染可能对受感染宿主的生物防御系统产生深远影响，尽管这种影响具有高度异质性。这种效应不仅由宿主与血吸虫的相互作用决定，而且还由寄生虫与寄生虫的相互作用决定。确定受感染宿主生物防御系统的复杂机制涉及宿主群体的疾病易感性，根除特定寄生虫可能会带来另一种传染病的意外风险。

项目成果

Ohta N, Yoshida A, Leafasia JL, Bobogare A, Kere N, Kirimaoma S, Tang L, Chen Y, Ohmae H & Ishii A.: "In : Malaria Research in the Solomon Islands" Inter Group Corp., 7 (1998)

Ohta N、Yoshida A、Leafasia JL、Bobogare A、Kere N、Kirimaoma S、Tang L、Chen Y、Ohmae H

Ohta N.: "Schistosomes as Th2 inducers. (Text in Japanese)" Journal of Clinical and Experimental Medicine. 183. 253-256 (1997)

Ohta N.：“血吸虫作为 Th2 诱导剂。（日语文本）”《临床与实验医学杂志》。

Zhang R, Takahashi S, Orita S, Yoshida A, Maruyama H, Shirai T & Ohta N.: "p53 gene mutations in rectal cancer associated with schistosomiasis japonica in Chinese patients." Cancer Letters. 131. 215-221 (1998)

张R，高桥S，奥田S，吉田A，丸山H，白井T

Yoshida A, Maruyama H, Yabu Y, Amano T & Ohta N.: "Immune responses against protozoal and nematodal infection in mice with underlying Schistosoma mansoni infection." Parasitology International. (in press).

吉田 A、丸山 H、Yabu Y、天野 T

太田伸生、 保坂幸男、 中島康雄、 荘和憲、 金澤保、 伊藤誠、 平山謙二、 薬袋勝、 周達人、 陳炎: "中国湖南省の日本住血吸虫病調査;揚子江流域の1村落をモデルとして" 熱帯. 30. 93-99 (1997)

Nobuo Ota、Yukio Hosaka、Yasuo Nakajima、Kazuken Zhuang、Tamotsu Kanazawa、Makoto Ito、Kenji Hirayyama、Masaru Yakubukuro、Tatsuren Zhou、Yan Chen：“中国湖南省日本血吸虫病调查；以长江流域的一个村庄为对象一个模型”热带。30. 93-99 (1997)