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

本研究旨在揭示蠕虫驱动的免疫调节对小鼠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优势状态，这可能对生物防御系统产生可检测的影响。本研究结果表明，血吸虫驱动的Th2反应诱导了对委内瑞拉圆线虫感染的强保护性免疫。另一方面，曼氏S.mansoni感染对利什曼原虫主要感染没有任何可检测到的影响，其中Th1反应在特定小鼠株中具有高度保护作用。C57BL/6小鼠通过诱导th1显性应答对L.major产生抗性，但即使同时感染S.mansoni， C57BL/6小鼠仍具有耐药性。在植入UV*1纤维肉瘤细胞的小鼠中，血吸虫驱动的Th2反应似乎损害了杀伤T细胞的反应。在对恰布迪疟原虫感染高度敏感的A/J小鼠中发现了意想不到的结果。当A/J型小鼠感染S.mansoni后，寄生虫病明显被抑制，并且没有小鼠死于疟疾，而单独感染P.chabaudi的A/J型小鼠在7 d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，尽管这种影响是高度异质性的。这种效应不仅由宿主-血吸虫相互作用决定，也由寄生虫-寄生虫相互作用决定。受感染宿主生物防御系统的复杂机制与宿主群体的疾病易感性有关，消灭特定寄生虫可能会带来意想不到的另一种传染病的风险。

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.