Nishikawa Y, Kawase O, Vielemeyer O, Suzuki H, Joiner K A, Xuan X, Nagasawa H
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido, Japan.
Parasite Immunol. 2007 Jul;29(7):375-85. doi: 10.1111/j.1365-3024.2007.00956.x.
Apoptosis has been found to help in the defence against pathogens. Infection with the obligate intracellular parasite Toxoplasma gondii is known to trigger host-cell apoptosis. When using a T. gondii-infected macrophage cell line, J774A.1, treatment with IFN-gamma significantly enhanced apoptosis in noninfected bystander cells while parasitized cells became relatively resistant. Infection and IFN-gamma treatment activated the expression of inducible nitric oxide synthase (iNOS), and the production of nitric oxide (NO) and treatment of cells with an iNOS inhibitor, N(G)-monomethlyl-L-arginine acetate (L-NMMA) reduced the apoptosis frequency. However, the reversal was only partial suggesting that not only NO, but also other, as of yet, unknown factors are induced. Finally, we studied the effect in vivo by infecting mice with either a virulent or an avirulent strain. Challenge with the virulent strain lead to a higher parasite burden, induced host-cell apoptosis in peritoneal cells, and produced higher levels of IFN-gamma and NO. Moreover, treatment of mice with a NO synthase inhibitor, aminoguanidine, partially inhibited the host-cell apoptosis induced by the parasite infection. Altogether, our findings indicate that apoptosis in bystander host cells is due to the secretion of NO and other soluble factors released by parasite-infected cells.
现已发现细胞凋亡有助于抵御病原体。已知专性细胞内寄生虫弓形虫感染会触发宿主细胞凋亡。在用弓形虫感染的巨噬细胞系J774A.1进行实验时，用γ干扰素处理可显著增强未感染的旁观者细胞的凋亡，而被寄生的细胞则相对具有抗性。感染和γ干扰素处理激活了诱导型一氧化氮合酶（iNOS）的表达，一氧化氮（NO）的产生，并且用iNOS抑制剂N（G）-单甲基-L-精氨酸乙酸盐（L-NMMA）处理细胞可降低凋亡频率。然而，这种逆转只是部分的，这表明不仅是NO，还有其他尚未知晓的因素也被诱导产生。最后，我们通过用强毒株或无毒株感染小鼠来研究体内效应。用强毒株攻击导致更高的寄生虫负荷，诱导腹膜细胞中的宿主细胞凋亡，并产生更高水平的γ干扰素和NO。此外，用一氧化氮合酶抑制剂氨基胍处理小鼠可部分抑制寄生虫感染诱导的宿主细胞凋亡。总之，我们的研究结果表明，旁观者宿主细胞中的凋亡是由于寄生虫感染细胞分泌的NO和其他可溶性因子所致。
