Human genetic basis of interindividual variability in the course of infection
Human genetic basis of interindividual variability in the course of infection
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DOI：
10.1073/pnas.1521644112
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发表时间：
2015-12-22
影响因子：
11.1
通讯作者：
Casanova, Jean-Laurent
中科院分区：
文献类型：
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作者：
Casanova, Jean-Laurent
人类传染病的关键问题是在20世纪初提出的：它们的发病机制。对于几乎任何给定的病毒，细菌，真菌或寄生虫，危及生命的临床疾病的发展，只有一小部分的感染者。解决这一感染之谜对临床诊断、预后、预防和治疗都具有重要意义。有些微生物将不可避免地对疫苗接种或化疗或两者都难以抵抗或逃避。这个解决方案在生物学上也很重要，因为真核生物的出现和进化，以及更快速进化的原核生物、古细菌和病毒的出现和进化，对生态和进化性质的免疫学提出了挑战。我们需要在自然条件下，而不是实验条件下，以及在分子和细胞水平上研究这些挑战。根据传染病的人类遗传理论，先天变异是威胁生命的传染病的基础。在这里，我回顾了从19世纪之交到20世纪下半叶人类传染病遗传学领域的历史。因此，本文设置的场景，提供所需的背景信息，以了解和欣赏最近描述的单基因形式的阻力或易感性，在第二篇论文中讨论的特定感染在这个问题。
The key problem in human infectious diseases was posed at the turn of the 20th century: their pathogenesis. For almost any given virus, bacterium, fungus, or parasite, life-threatening clinical disease develops in only a small minority of infected individuals. Solving this infection enigma is important clinically, for diagnosis, prognosis, prevention, and treatment. Some microbes will inevitably remain refractory to, or escape vaccination, or chemotherapy, or both. The solution also is important biologically, because the emergence and evolution of eukaryotes alongside more rapidly evolving prokaryotes, archaea, and viruses posed immunological challenges of an ecological and evolutionary nature. We need to study these challenges in natural, as opposed to experimental, conditions, and also at the molecular and cellular levels. According to the human genetic theory of infectious diseases, inborn variants underlie life-threatening infectious diseases. Here I review the history of the field of human genetics of infectious diseases from the turn of the 19th century to the second half of the 20th century. This paper thus sets the scene, providing the background information required to understand and appreciate the more recently described monogenic forms of resistance or predisposition to specific infections discussed in a second paper in this issue.