Brites Daniela, Gagneux Sebastien
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute and University of Basel, Basel, Switzerland.
Immunol Rev. 2015 Mar;264(1):6-24. doi: 10.1111/imr.12264.
The causative agent of human tuberculosis (TB), Mycobacterium tuberculosis, is an obligate pathogen that evolved to exclusively persist in human populations. For M. tuberculosis to transmit from person to person, it has to cause pulmonary disease. Therefore, M. tuberculosis virulence has likely been a significant determinant of the association between M. tuberculosis and humans. Indeed, the evolutionary success of some M. tuberculosis genotypes seems at least partially attributable to their increased virulence. The latter possibly evolved as a consequence of human demographic expansions. If co-evolution occurred, humans would have counteracted to minimize the deleterious effects of M. tuberculosis virulence. The fact that human resistance to infection has a strong genetic basis is a likely consequence of such a counter-response. The genetic architecture underlying human resistance to M. tuberculosis remains largely elusive. However, interactions between human genetic polymorphisms and M. tuberculosis genotypes have been reported. Such interactions are consistent with local adaptation and allow for a better understanding of protective immunity in TB. Future 'genome-to-genome' studies, in which locally associated human and M. tuberculosis genotypes are interrogated in conjunction, will help identify new protective antigens for the development of better TB vaccines.
人类结核病（TB）的病原体结核分枝杆菌是一种专性病原体，它进化到仅在人类群体中持续存在。为了在人与人之间传播，结核分枝杆菌必须引发肺部疾病。因此，结核分枝杆菌的毒力很可能是结核分枝杆菌与人类关联的一个重要决定因素。事实上，一些结核分枝杆菌基因型的进化成功似乎至少部分归因于它们毒力的增强。后者可能是人类人口扩张的结果。如果发生了共同进化，人类会采取对策以尽量减少结核分枝杆菌毒力的有害影响。人类对感染的抵抗力具有强大的遗传基础这一事实可能就是这种反作用的结果。人类对结核分枝杆菌抵抗力的遗传结构在很大程度上仍然难以捉摸。然而，已经报道了人类基因多态性与结核分枝杆菌基因型之间的相互作用。这种相互作用与局部适应性一致，有助于更好地理解结核病的保护性免疫。未来将本地相关的人类和结核分枝杆菌基因型结合起来进行研究的“基因组对基因组”研究，将有助于识别新的保护性抗原，以开发更好的结核病疫苗。
Zotero 插件
