Dost C K, Saraiva J, Zentgraf U, Monesi N, Engels W, Albuquerque S
Lehrstuhl Allgemeine Genetik, ZMBP, University of Tübingen.
J Infect. 2006 Jan;52(1):49-55. doi: 10.1016/j.jinf.2005.02.003.
Trypanosoma cruzi, the agent of Chagas disease, is known to cause enhanced nitric oxide (NO) production, which might be involved in host resistance. The inducible nitric-oxide-synthase (iNOS) is assumed to be responsible for the NO increase after several infections. We studied the potential role of NO in Calomys callosus, a natural reservoir of this protozoan parasite. The concentration of NO was determined in spleen and liver of animals infected with two different T. cruzi strains, BOL and BOL-SB. Furthermore, the iNOS mRNA expression was quantified in the same cell types. NO production was detectable in both tissues exhibiting only slight differences compared to non-infected controls. All measured NO values were significantly lower than those reported for a number of different mouse strains, which displayed extremely enhanced NO levels after T. cruzi infection. Surprisingly, iNOS mRNA expression was induced in infected C. callosus but without subsequent increase of NO levels, indicating a post-transcriptional regulation mechanism. In summary, our results, indicate that the tolerance of C. callosus to T. cruzi is only accompanied by non-toxic NO intracellular concentrations.
克氏锥虫是恰加斯病的病原体,已知其会导致一氧化氮(NO)生成增加,这可能与宿主抵抗力有关。诱导型一氧化氮合酶(iNOS)被认为是多种感染后NO增加的原因。我们研究了NO在这种原生动物寄生虫的天然宿主——南美原鼠中的潜在作用。测定了感染两种不同克氏锥虫菌株BOL和BOL-SB的动物脾脏和肝脏中的NO浓度。此外,还对相同细胞类型中的iNOS mRNA表达进行了定量分析。在两个组织中均检测到了NO生成,与未感染的对照组相比,差异仅很微小。所有测得的NO值均显著低于许多不同小鼠品系所报告的值,这些小鼠品系在感染克氏锥虫后NO水平极度升高。令人惊讶的是,感染的南美原鼠中iNOS mRNA表达被诱导,但随后NO水平并未升高,这表明存在转录后调控机制。总之,我们的结果表明,南美原鼠对克氏锥虫的耐受性仅伴随着无毒的细胞内NO浓度。