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

这项研究是为了揭示蠕虫驱动的免疫调节对小鼠其他无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占优势的状态，这可能对生物防御系统产生明显的影响。本研究结果提示，血吸虫Th2免疫应答可诱导机体产生较强的保护性免疫。另一方面，曼氏血吸虫感染对利什曼原虫的主要感染没有任何可检测到的影响，而Th1反应对特定的小鼠品系具有高度的保护作用。C57BL/6小鼠通过诱导Th1显性应答对大鼠产生抵抗力，但即使同时感染曼氏血吸虫，这些小鼠仍具有抵抗力。在植入UV*1纤维肉瘤细胞的小鼠中，血吸虫驱动的Th2反应似乎削弱了杀伤T细胞反应。在A/J小鼠感染查鲍迪疟原虫的情况下观察到了意想不到的结果，这是对查鲍迪疟原虫感染高度敏感的。A/J小鼠感染曼氏血吸虫后，原虫血症明显受到抑制，无一只小鼠死于疟疾，而单独感染沙包氏血吸虫的A/J小鼠在7天内全部死亡。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刻影响，尽管这些影响是高度异质性的。这种影响不仅由宿主-血吸虫相互作用决定，也由寄生虫-寄生虫相互作用决定。确定受感染宿主的生物防御系统的复杂机制与宿主群体的疾病易感性有关，根除特定的寄生虫可能会带来另一种感染性疾病的意外风险。

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.