Cummings Kara L, Tarleton Rick L
Center for Tropical and Emerging Global Diseases, 623 Biological Sciences Building, University of Georgia, Athens, GA 30602, USA.
Infect Immun. 2004 Jul;72(7):4081-9. doi: 10.1128/IAI.72.7.4081-4089.2004.
Immune control of many intracellular pathogens, including Trypanosoma cruzi, is reported to be dependent on the production of nitric oxide. In this study, we show that mice deficient in inducible nitric oxide synthase (iNOS or NOS2) exhibit resistance to T. cruzi infection that is comparable to that of wild-type mice. This is the case for two iNOS-deficient mouse strains, Nos2(tm1Lau) and Nos2 N5, infected with the Brazil or Tulahuen strain of T. cruzi. In all cases, blood parasitemia, tissue parasite load, and survival rates are similar between wild-type and iNOS-deficient mice. In contrast, both wild-type and Nos2(tm1Lau) mice died within 32 days postinfection when treated with the nitric oxide synthase inhibitor aminoguanidine. Increased transcription of NOS1 or NOS3 is not found in iNOS-knockout (KO) mice, indicating that the absence of nitric oxide production through iNOS is not compensated for by increased production of other NOS isoforms. However, Nos2(tm1Lau) mice exhibit enhanced expression of tumor necrosis factor alpha, interleukin-1, and macrophage inflammatory protein 1alpha compared to that of wild-type mice, and these alterations may in part compensate for the lack of iNOS. These results clearly show that iNOS is not required for control of T. cruzi infection in mice.
据报道，包括克氏锥虫在内的许多细胞内病原体的免疫控制依赖于一氧化氮的产生。在本研究中，我们发现诱导型一氧化氮合酶（iNOS或NOS2）缺陷的小鼠对克氏锥虫感染表现出与野生型小鼠相当的抵抗力。感染巴西株或图拉韦恩株克氏锥虫的两种iNOS缺陷小鼠品系Nos2(tm1Lau)和Nos2 N5就是这种情况。在所有情况下，野生型和iNOS缺陷小鼠之间的血中寄生虫血症、组织寄生虫负荷和存活率相似。相比之下，野生型和Nos2(tm1Lau)小鼠在用一氧化氮合酶抑制剂氨基胍治疗后，在感染后32天内死亡。在iNOS基因敲除（KO）小鼠中未发现NOS1或NOS3转录增加，这表明iNOS产生一氧化氮的缺失并未被其他NOS同工型的增加所补偿。然而，与野生型小鼠相比，Nos2(tm1Lau)小鼠表现出肿瘤坏死因子α、白细胞介素-1和巨噬细胞炎性蛋白1α的表达增强，这些改变可能部分补偿了iNOS的缺乏。这些结果清楚地表明，iNOS对于小鼠控制克氏锥虫感染不是必需的。
