Genetic control of natural resistance to nontuberculous mycobacterial infections in mice.
Genetic control of natural resistance to nontuberculous mycobacterial infections in mice.
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小鼠对非结核分枝杆菌感染自然抵抗力的遗传控制。
DOI：
10.1128/iai.54.1.56-62.1986
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发表时间：
1986
影响因子：
3.1
通讯作者：
Collins,FM
中科院分区：
文献类型：
--
作者：
Orme,IM;Stokes,RW;Collins,FM
结果表明，根据实验性静脉感染后多种非结核分枝杆菌感染在靶器官中生长的能力，各种近交系小鼠可以分为两个不同的组。第一组允许这些感染逐渐增长，因此被指定为自然易受这些感染的人群；相反，那些能够发挥可检测到的抑菌作用的菌株被指定为天然耐药菌株。随后发现，基于这种区别的小鼠品系的分离也反映了这些动物对分枝杆菌感染产生获得性免疫力的能力。例如，类分枝杆菌在易感的 C57BL/6 小鼠中逐渐生长，随后触发获得性免疫机制，而在感染该生物体的抗性 A/Tru 小鼠中，没有发现获得性免疫的证据。排除了后一种菌株由于巨噬细胞活化缺陷而无法表达获得性免疫的可能性。此外，发现对这些感染的抵抗性特征可以通过骨髓细胞转移到辐射嵌合体中，从而表明该特征由造血前体细胞的后代表达。随后的回交分析确定了对这些分枝杆菌感染的抗性性状的遗传模式，所揭示的数据与这种抗性由多个基因控制的假设相一致。通过最大似然法对数据进行统计分析表明多基因控制，尽管在某些情况下概率值表明受修饰基因影响的主基因控制。这些发现表明，之前的假设，即近交系小鼠中分枝杆菌感染的生长是由单个基因控制的，应该重新评估。
Results show that various inbred strains of mice can be segregated into two distinct groups, based on their capacity to allow a number of nontuberculous mycobacterial infections to grow in target organs following experimental intravenous infection. The first group, which allowed these infections to grow progressively, was thus designated as naturally susceptible to these infections; in contrast, those strains which were able to exert detectable bacteriostasis were designated as naturally resistant. It was then found that segregation of mouse strains based on this distinction also mirrored the capacity of these animals to generate acquired immunity to the mycobacterial infections. For example, Mycobacterium simiae grew progressively in susceptible C57BL/6 mice, subsequently triggering acquired mechanisms of immunity, whereas no evidence for acquired immunity could be found in resistant A/Tru mice infected with this organism. The possibility that acquired immunity could not be expressed in the latter strain as a result of a defect in macrophage activation was excluded. Moreover, it was found that the trait of resistance to these infections could be transferred by bone marrow cells into radiation chimeras, thus indicating that this trait was expressed by the progeny of hemopoietic precursor cells. Subsequent backcross analysis to determine the mode of inheritance of the trait of resistance to these mycobacterial infections revealed data that were consistent with the hypothesis that this resistance is controlled by more than one gene. Statistical analysis of the data by the maximum likelihood method suggested polygenic control, although in some cases the probability values suggested control by a major gene, influenced by modifier genes. These findings suggest that the previous hypothesis that the growth of mycobacterial infections in inbred strains of mice is controlled by a single gene should be reevaluated.