Helminth Coinfection Does Not Affect Therapeutic Effect of a DNA Vaccine in Mice Harboring Tuberculosis
Helminth Coinfection Does Not Affect Therapeutic Effect of a DNA Vaccine in Mice Harboring Tuberculosis
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DOI：
10.1371/journal.pntd.0000700
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发表时间：
2010-06-01
影响因子：
3.8
通讯作者：
Faccioli, Lucia H.
中科院分区：
文献类型：
--
作者：
Frantz, Fabiani G.;Rosada, Rogerio S.;Faccioli, Lucia H.
背景资料：蠕虫病和结核病（TB）在地理上是一致的，并且人们对探索并发蠕虫感染如何改变对杆菌的免疫反应以及可能需要改变治疗方法非常感兴趣。编码M.麻风（DNAhsp 65）已被用于实验性结核病的治疗。本研究旨在探讨蠕虫与蛔虫共存对DNAhsp 65治疗效果的影响。方法：用犬弓首线虫或曼氏血吸虫感染小鼠，然后再感染曼氏血吸虫。结核病和DNAhsp 65治疗。而T.犬感染并不增加肺结核的易感性，S. mansoni增强了对TB的易感性，如肺和脾中细菌数量增加所示，这与Th 2和调节细胞因子的增加有关。然而，在共感染的小鼠中，DNAhsp 65的治疗效果并没有被废除，如集落形成单位和组织病理学变化分析所示。体外研究表明，Hsp 65特异性IFN-γ的产生与疫苗诱导的保护作用有关。此外，在S.曼氏菌共感染的小鼠，DNA治疗抑制体内TGF-β和IL-10的生产，这可能与长期protection.Conclusions/Significance：我们已经证明，在实验性TB感染中的DNAhsp 65的治疗效果是持久的存在下，一个无关的Th 2免疫反应诱导蠕虫感染。
Background: 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.