Barbour Alan G, Duong Jonathan V, Long Anthony D
Department of Microbiology & Molecular Genetics, School of Medicine, University of California Irvine, Irvine, CA 92697, USA.
Department of Medicine, School of Medicine, University of California Irvine, Irvine, CA 92697, USA.
Pathogens. 2023 Aug 18;12(8):1056. doi: 10.3390/pathogens12081056.
The abundant and widely distributed deermice and are important reservoirs for several different zoonotic agents in North America. For the pathogens they persistently harbor, these species are also examples of the phenomenon of infection tolerance. In the present study a prior observation of absent expression of the high-affinity Fc immunoglobulin gamma receptor I (FcγRI), or CD64, in was confirmed in an experimental infection with , a Lyme disease agent. We demonstrate that the null phenotype is attributable to a long-standing inactivation of the Fcgr1 gene in both species by a deletion of the promoter and coding sequence for the signal peptide for FcγRI. The Fcgr1 pseudogene was also documented in the related species . Six other species, including , have coding sequences for a full-length FcγRI, including a consensus signal peptide. An inference from reported phenotypes for null Fcgr1 mutations engineered in is that one consequence of pseudogenization of Fcgr1 is comparatively less inflammation during infection than in animals, including humans, with undisrupted, fully active genes.
数量众多且分布广泛的鹿鼠是北美几种不同人畜共患病原体的重要宿主。对于它们持续携带的病原体而言，这些物种也是感染耐受现象的例证。在本研究中，先前观察到的高亲和力Fc免疫球蛋白γ受体I（FcγRI）即CD64在[具体物种]中不表达的现象，在感染莱姆病病原体[具体病原体]的实验中得到了证实。我们证明，这种无效表型归因于这两个物种中Fcgr1基因长期失活，原因是FcγRI信号肽的启动子和编码序列缺失。在相关物种[具体物种]中也记录到了Fcgr1假基因。包括[具体物种]在内的其他六个[具体物种]具有全长FcγRI的编码序列，包括一个共有信号肽。根据在[具体物种]中设计的Fcgr1无效突变的报告表型推断，Fcgr1基因假基因化的一个后果是，与具有未中断的、完全活跃基因的动物（包括人类）相比，感染期间的炎症相对较少。
