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Murine models of Salmonella enterica serovar Typhimurium infection are one of the commonest tools to study host-pathogen interactions during bacterial infections. Critically, the outcome of S. Typhimurium infection is impacted by the genetic background of the mouse strain used, with macrophages from C57BL/6 and BALB/c mice lacking the capacity to control intracellular bacterial replication. For this reason, the use of congenic strains, which mix the genetic backgrounds of naturally protected mouse strains with those of susceptible strains, has the capacity to significantly alter results and interpretation of S. Typhimurium infection studies. Here, we describe how macrophage knockout cell lines generated by CRISPR/Cas9 gene editing can help determine the contribution of background contaminations in the phenotypes of primary macrophages from congenic mice, on the outcome of S. Typhimurium infection studies. Our own experience illustrates how the CRISPR/Cas9 technology can be used to complement pre-existing knockout models, and shows that there is great merit in performing concurrent studies with both genetic models, to exclude unanticipated side-effects on host-pathogen interactions.

鼠伤寒沙门氏菌（Salmonella enterica serovar Typhimurium）感染小鼠模型是研究细菌感染过程中宿主-病原体相互作用的最常用工具之一。至关重要的是，鼠伤寒沙门氏菌感染的结局受所用小鼠品系的遗传背景影响：C57BL/6与BALB/c小鼠的巨噬细胞无法控制胞内细菌增殖。正因如此，整合天然抗性小鼠品系与易感品系遗传背景的同类系小鼠（congenic strains）的应用，可能会显著改变鼠伤寒沙门氏菌感染研究的结果与解读。本文阐述了经CRISPR/Cas9基因编辑（CRISPR/Cas9 gene editing）构建的巨噬细胞基因敲除细胞系，如何助力解析同类系小鼠原代巨噬细胞表型中的背景混杂因素对鼠伤寒沙门氏菌感染研究结局的影响。我们的研究经验表明，CRISPR/Cas9技术可用于补充已有的基因敲除模型，且同时采用两类遗传模型开展研究以排除对宿主-病原体相互作用的未预期副作用，具有重要的研究价值。