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中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处于Th 2型优势状态，可能对生物防御系统产生可检测的影响。本研究的结果表明，血吸虫驱动的Th 2反应诱导了针对委内瑞拉圆线虫感染的强大保护性免疫。另一方面，曼氏血吸虫感染对主要利什曼原虫感染没有任何可检测的影响，Th 1应答在特定小鼠品系中具有高度保护性。C57 BL/6小鼠通过诱导Th 1-显性应答对硕大志贺菌产生抗性，然而，这些小鼠即使在曼氏血吸虫的伴随感染中仍然具有抗性。在植入UV*1纤维肉瘤细胞的小鼠中，血吸虫驱动的Th 2应答似乎削弱了杀伤T细胞应答。在对夏氏疟原虫感染高度易感的A/J小鼠中夏氏疟原虫感染的情况下观察到意外结果。当用曼氏血吸虫感染A/J小鼠时，寄生虫血症被显著抑制，并且没有小鼠死于疟疾，而仅用夏氏疟原虫感染的所有A/J小鼠在7天内死亡。与这些结果一起，我们得出结论，尽管这种影响是高度异质性的，但寄生虫感染可能对受感染宿主的生物防御系统产生深刻的影响。这种效应不仅由宿主-寄生体相互作用决定，而且由寄生物-寄生物相互作用决定。决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，并且特定寄生虫的根除可能提供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.