Praziquantel Targets M1 Macrophages and Ameliorates Splenomegaly in Chronic Schistosomiasis
Praziquantel Targets M1 Macrophages and Ameliorates Splenomegaly in Chronic Schistosomiasis
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吡喹酮靶向 M1 巨噬细胞并改善慢性血吸虫病的脾肿大
DOI：
10.1128/aac.00005-17
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发表时间：
2018-01-01
影响因子：
4.9
通讯作者：
Wang, Yong
中科院分区：
文献类型：
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作者：
Kong, Delong;Zhou, Chunlei;Wang, Yong
脾肿大是许多传染病的共同特征，包括日本血吸虫病。然而，血吸虫病脾肿大的免疫发病机制和治疗一直被忽视。吡喹酮（PZQ）是一种经典的抗血吸虫药，已被我们和其他人证明具有抗血吸虫病纤维化和抗炎活性。本研究观察了吡喹酮对日本血吸虫感染小鼠脾肿大的影响。结果表明，巨噬细胞数量在感染小鼠肿大的脾脏中明显增多，尤其是M1巨噬细胞数量明显增多（P < 0.001）。PZQ治疗4周后，脾巨噬细胞，尤其是M1巨噬细胞数量明显减少（P < 0.001），其途径是凋亡，而甲氟喹对脾肿大和巨噬细胞数量减少均无影响。此外，通过使用小鼠巨噬细胞系RAW 264.7，我们发现PZQ可以抑制M1巨噬细胞中NLRP 3炎性小体的形成并减弱吞噬活性。因此，我们的研究表明，PZQ在改善S.日本血吸虫感染，这为治疗其他病理条件引起的脾肿大提供了新的策略。
Splenomegaly is a common feature of many infectious diseases, including schistosomiasis japonica. However, the immunopathogenesis and the treatment of splenomegaly due to schistosomiasis have been largely neglected. Praziquantel (PZQ), a classical schistosomicide, has been demonstrated by us and others to have antifibrotic and anti-inflammatory activities against schistosomiasis. In this study, we investigated the effect of PZQ on alleviating the splenomegaly caused by Schistosoma japonicum infection in mice. The results showed that the number of macrophages, especially the number of M1 macrophages, was significantly increased in the enlarged spleens of infected mice (P < 0.001). After PZQ treatment for 4 weeks, the number of splenic macrophages, especially the number of M1 macrophages, was significantly reduced (P < 0.001) by the way of apoptosis, and another schistosomicide, mefloquine, had no effect either on the splenomegaly or on reducing the number of macrophages. Furthermore, by using the murine macrophage line RAW 264.7, we found that PZQ could inhibit the formation of the NLRP3 inflammasome and attenuate phagocytic activity in M1 macrophages. Thus, our studies suggest that PZQ plays a powerful role in ameliorating the splenomegaly caused by S. japonicum infection, which presents a new strategy for the therapy of splenomegaly resulting from other pathological conditions.