Role of IFN-gamma in lethal and nonlethal malaria in susceptible and resistant murine hosts.
Role of IFN-gamma in lethal and nonlethal malaria in susceptible and resistant murine hosts.
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DOI：
10.4049/jimmunol.143.6.2038
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发表时间：
1989-09
影响因子：
4.4
通讯作者：
H. Shear;R. Srinivasan;T. Nolan;C. Ng
中科院分区：
文献类型：
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作者：
H. Shear;R. Srinivasan;T. Nolan;C. Ng
IFN-γ在宿主防御微生物疾病中起重要作用。在这里，我们研究了IFN-γ在致死性和非致死性鼠疟疾中的作用。重组鼠IFN-γ的管理导致SW，BALB/cByJ和CBA/J小鼠的剂量依赖性保护约氏疟原虫17 x（PyL）的致死性变体，但对该寄生虫（PyNL）的非致死性变体的过程几乎没有影响。体外测量显示，重组IFN-γ的给药还导致腹腔巨噬细胞活化，增加对疟疾感染红细胞的吞噬作用和H2 O2的释放。还研究了来自感染小鼠的脾细胞在疟疾过程中产生内源性IFN-γ和释放H2 O2的能力。在对PyL和PyNL相对敏感的BALB/cByJ小鼠中，仅响应于PyNL存在IFN-γ的初始爆发，而在对这些寄生虫相对抗性的CBA/J小鼠中，响应于PyL和PyNL两者存在IFN-γ的初始爆发。H2 O2释放的动力学对应于IFN-γ的动力学。在所有感染，IFN-γ水平下降，寄生虫血症增加，然而，非致死性感染的特点是恢复IFN-γ活性和H2 O2释放寄生虫血症下降。这些数据表明，IFN-γ可能在调节疟疾感染的过程中发挥重要作用，通过激活巨噬细胞的细胞内和细胞外寄生虫破坏。
IFN-gamma plays an important role in host defense against microbial disease. Here, we studied the role of IFN-gamma in lethal and nonlethal murine malaria. Administration of recombinant murine IFN-gamma resulted in a dose-dependent protection of SW, BALB/cByJ, and CBA/J mice from the lethal variant of Plasmodium yoelii 17x (PyL) but had little effect on the course of the nonlethal variant of this parasite (PyNL). Administration of recombinant IFN-gamma also resulted in the activation of peritoneal macrophages for increased phagocytosis of malaria-infected erythrocytes and release of H2O2, as measured in vitro. The ability of spleen cells from infected mice to produce endogenous IFN-gamma and release H2O2 during the course of malaria was also studied. In BALB/cByJ mice, which are relatively susceptible to PyL and PyNL, there was an initial burst of IFN-gamma only in response to PyNL whereas in CBA/J mice, which are relatively resistant to these parasites, there was an initial burst of IFN-gamma in response to both PyL and PyNL. The kinetics of H2O2 release corresponded to that of IFN-gamma. In all infections, levels of IFN-gamma declined as parasitemia increased; however, nonlethal infections were characterized by a recovery of both IFN-gamma activity and H2O2 release as parasitemia declined. These data suggest that IFN-gamma may play an important role in modulating the course of malaria infections by activating macrophages for both intracellular and extracellular parasite destruction.