Consequences of immunopathology for pathogen virulence evolution and public health: malaria as a case study
Consequences of immunopathology for pathogen virulence evolution and public health: malaria as a case study
复制标题
DOI：
10.1111/j.1752-4571.2010.00178.x
复制
发表时间：
2011-03-01
影响因子：
4.1
通讯作者：
Graham, Andrea L.
中科院分区：
文献类型：
--
作者：
Long, Grainne H.;Graham, Andrea L.
解释毒力（受感染宿主造成的适应性损害）的进化理论通常关注宿主内部利用的寄生虫策略。然而，许多毒力可能是由宿主自身的免疫反应引起的：例如，促炎细胞因子虽然对于杀死疟疾寄生虫至关重要，但也会损害宿主组织。在这里，我们认为免疫介导的毒力或“免疫病理学”可能会影响疟疾毒力的进化，在设计医疗干预措施时应予以考虑。我们的论点是基于免疫病理学破坏毒力进化权衡理论假设的正毒力传播关系的能力。在啮齿动物疟疾感染期间，使用批准用于现场使用的试剂进行实验性减少炎症会降低毒力，但会增加寄生虫传播的可能性。重要的是，啮齿动物疟原虫在诱发炎症的倾向上表现出遗传多样性，并在促炎细胞因子存在的情况下形成传播阶段的寄生虫。如果免疫病理学与疟疾寄生虫密度呈正相关，理论上表明它可以选择相对较低的疟疾毒力。因此，降低免疫病理学的医疗干预可能会无意中选择增加疟疾毒力。必须更好地理解免疫病理学变化对寄生虫的适应性影响，以便预测异质宿主群体中寄生虫毒力进化的轨迹以及对医疗干预的反应。
Evolutionary theories explaining virulence-the fitness damage incurred by infected hosts-often focus on parasite strategies for within-host exploitation. However, much virulence can be caused by the host's own immune response: for example, pro-inflammatory cytokines, although essential for killing malaria parasites, also damage host tissue. Here we argue that immune-mediated virulence, or 'immunopathology,' may affect malaria virulence evolution and should be considered in the design of medical interventions. Our argument is based on the ability of immunopathology to disrupt positive virulence-transmission relationships assumed under the trade-off theory of virulence evolution. During rodent malaria infections, experimental reduction of inflammation using reagents approved for field use decreases virulence but increases parasite transmission potential. Importantly, rodent malaria parasites exhibit genetic diversity in the propensity to induce inflammation and invest in transmission-stage parasites in the presence of pro-inflammatory cytokines. If immunopathology positively correlates with malaria parasite density, theory suggests it could select for relatively low malaria virulence. Medical interventions which decrease immunopathology may therefore inadvertently select for increased malaria virulence. The fitness consequences to parasites of variations in immunopathology must be better understood in order to predict trajectories of parasite virulence evolution in heterogeneous host populations and in response to medical interventions.