Laboratory of Mycobacterial Immunity and Pathogenesis, Rutgers, The State University of New Jersey, 225 Warren Street, Newark, NJ 07103, USA.
Public Health Research Institute at Rutgers Biomedical and Health Sciences, Rutgers, The State University of New Jersey, 225 Warren Street, Newark, NJ 07103, USA.
J Immunol Res. 2015;2015:385402. doi: 10.1155/2015/385402. Epub 2015 Aug 3.
Mycobacterium tuberculosis the causative agent of tuberculosis affects millions of people worldwide. New tools for treatment and prevention of tuberculosis are urgently needed. We previously showed that a ferritin (bfrB) mutant of M. tuberculosis has altered iron homeostasis and increased sensitivity to antibiotics and to microbicidal effectors produced by activated macrophages. Most importantly, M. tuberculosis lacking BfrB is strongly attenuated in mice, especially, during the chronic phase of infection. In this study, we examined whether immunization with a bfrB mutant could confer protection against subsequent infection with virulent M. tuberculosis in a mouse model. The results show that the protection elicited by immunization with the bfrB mutant is comparable to BCG vaccination with respect to reduction of bacterial burden. However, significant distinctions in the disease pathology and host genome-wide lung transcriptome suggest improved containment of Mtb infection in animals vaccinated with the bfrB mutant, compared to BCG. We found that downmodulation of inflammatory response and enhanced fibrosis, compared to BCG vaccination, is associated with the protective response elicited by the bfrB mutant.
结核分枝杆菌是结核病的病原体，影响着全球数百万人。目前迫切需要新的结核病治疗和预防工具。我们之前曾表明，结核分枝杆菌的铁蛋白（bfrB）突变体能改变铁稳态，并增加对抗生素和活化巨噬细胞产生的杀菌效应物的敏感性。最重要的是，缺乏 BfrB 的结核分枝杆菌在小鼠中高度减毒，特别是在感染的慢性期。在这项研究中，我们研究了用 bfrB 突变体免疫是否可以在小鼠模型中提供针对随后感染毒力结核分枝杆菌的保护。结果表明，bfrB 突变体免疫引发的保护作用在降低细菌负荷方面与卡介苗接种相当。然而，疾病病理学和宿主全肺转录组的显著差异表明，与卡介苗相比，用 bfrB 突变体接种疫苗的动物中，结核分枝杆菌感染得到了更好的控制。我们发现，与卡介苗接种相比，炎症反应的下调和纤维化的增强与 bfrB 突变体引发的保护性反应有关。
