Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Department of Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, USA.
Infect Immun. 2018 Jan 22;86(2). doi: 10.1128/IAI.00636-17. Print 2018 Feb.
In every epidemic some individuals become sick and some may die, whereas others recover from illness and still others show no signs or symptoms of disease. These differences highlight a fundamental question of microbial pathogenesis: why are some individuals susceptible to infectious diseases while others who acquire the same microbe remain well? For most of human history, the answer assumed the hand of providence. With the advent of the germ theory of disease, the focus on disease causality became the microbe, but this did not explain how there can be different outcomes of infection in different individuals with the same microbe. Here we examine the attributes of susceptibility in the context of the "damage-response framework" of microbial pathogenesis. We identify 11 attributes that, although not independent, are sufficiently distinct to be considered separately: microbiome, inoculum, sex, temperature, environment, age, chance, history, immunity, nutrition, and genetics. We use the first letter of each to create the mnemonic MISTEACHING, underscoring the need for caution in accepting dogma and attributing disease causality to any single factor. For both populations and individuals, variations in the attributes that assemble into MISTEACHING can create an enormity of combinations that can in turn translate into different outcomes of host-microbe encounters. Combinatorial diversity among the 11 attributes makes identifying "signatures" of susceptibility possible. However, with their inevitable uncertainties and propensity to change, there may still be a low likelihood for prediction with regard to individual host-microbe interactions, although probabilistic prediction may be possible.
在每一次疫情中,有些个体患病并可能死亡,而有些则从疾病中康复,还有些则没有疾病的迹象或症状。这些差异突出了一个微生物发病机制的基本问题:为什么有些人容易感染传染病,而有些人感染相同的微生物却保持健康?在人类历史的大部分时间里,答案都归因于天意。随着疾病的细菌理论的出现,对疾病因果关系的关注转向了微生物,但这并不能解释为什么在相同的微生物感染下,不同个体的感染结果会有所不同。在这里,我们在微生物发病机制的“损伤-反应框架”的背景下研究易感性的属性。我们确定了 11 个属性,尽管它们不是独立的,但足以区分开来,可以分别考虑:微生物组、接种物、性别、温度、环境、年龄、机会、历史、免疫、营养和遗传。我们用每个属性的首字母创建了助记符 MISTEACHING,强调在接受教条和将疾病因果关系归因于任何单一因素时需要谨慎。对于人群和个体来说,组装成 MISTEACHING 的属性的变化可以产生巨大的组合,从而转化为宿主-微生物相遇的不同结果。11 个属性之间的组合多样性使得确定易感性“特征”成为可能。然而,由于其不可避免的不确定性和变化倾向,尽管可能进行概率预测,但对于个体宿主-微生物相互作用的预测仍然不太可能。