Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
PLoS Negl Trop Dis. 2010 Jun 8;4(6):e700. doi: 10.1371/journal.pntd.0000700.
Helminthiasis and tuberculosis (TB) coincide geographically and there is much interest in exploring how concurrent worm infections might alter immune responses against bacilli and might necessitate altered therapeutic approaches. A DNA vaccine that codifies heat shock protein Hsp65 from M. leprae (DNAhsp65) has been used in therapy during experimental tuberculosis. This study focused on the impact of the co-existence of worms and TB on the therapeutic effects of DNAhsp65.
METHODOLOGY/PRINCIPAL FINDINGS: Mice were infected with Toxocara canis or with Schistosoma mansoni, followed by coinfection with M. tuberculosis and treatment with DNAhsp65. While T. canis infection did not increase vulnerability to pulmonary TB, S. mansoni enhanced susceptibility to TB as shown by higher numbers of bacteria in the lungs and spleen, which was associated with an increase in Th2 and regulatory cytokines. However, in coinfected mice, the therapeutic effect of DNAhsp65 was not abrogated, as indicated by colony forming units and analysis of histopathological changes. In vitro studies indicated that Hsp65-specific IFN-gamma production was correlated with vaccine-induced protection in coinfected mice. Moreover, in S. mansoni-coinfected mice, DNA treatment inhibited in vivo TGF-beta and IL-10 production, which could be associated with long-term protection.
CONCLUSIONS/SIGNIFICANCE: We have demonstrated that the therapeutic effects of DNAhsp65 in experimental TB infection are persistent in the presence of an unrelated Th2 immune response induced by helminth infections.
寄生虫病和结核病（TB）在地理上同时存在，人们对探索同时感染蠕虫是否会改变针对杆菌的免疫反应以及是否需要改变治疗方法非常感兴趣。一种编码麻风分枝杆菌热休克蛋白 Hsp65 的 DNA 疫苗（DNAhsp65）已在实验性结核病的治疗中使用。本研究重点研究蠕虫和 TB 的共存对 DNAhsp65 治疗效果的影响。
方法/主要发现：用旋毛线虫或曼氏血吸虫感染小鼠，然后与结核分枝杆菌共同感染，并接受 DNAhsp65 治疗。旋毛线虫感染不会增加对肺 TB 的易感性，而曼氏血吸虫感染会增加对 TB 的易感性，表现为肺部和脾脏中的细菌数量增加，这与 Th2 和调节细胞因子的增加有关。然而，在共感染的小鼠中，DNAhsp65 的治疗效果并未被削弱，这表明 CFU 和组织病理学变化分析。体外研究表明，Hsp65 特异性 IFN-γ 产生与共感染小鼠中疫苗诱导的保护相关。此外，在曼氏血吸虫共感染的小鼠中，DNA 处理抑制了体内 TGF-β 和 IL-10 的产生，这可能与长期保护有关。
结论/意义：我们已经证明，在由蠕虫感染引起的无关 Th2 免疫反应存在的情况下，DNAhsp65 在实验性 TB 感染中的治疗效果是持续的。
