Usp18 Expression in CD169+ Macrophages is Important for Strong Immune Response after Vaccination with VSV-EBOV
Usp18 Expression in CD169+ Macrophages is Important for Strong Immune Response after Vaccination with VSV-EBOV
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DOI：
10.3390/vaccines8010142
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发表时间：
2020-03-01
期刊：
影响因子：
7.8
通讯作者：
Lang, Karl Sebastian
中科院分区：
文献类型：
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作者：
Friedrich, Sarah-Kim;Schmitz, Rosa;Lang, Karl Sebastian
由于VSV-EBOV疫苗(Ervebo)具有快速的保护能力，可以有效地控制埃博拉病毒的流行，但副作用阻碍了VSV-EBOV作为疫苗的广泛使用。解释单次注射VSV-EBOV疫苗后有效免疫激活的机制主要尚不清楚。在这里，使用临床上可用的VSV-EBOV疫苗(Ervebo)，我们发现干扰素抑制物Usp18在CD169(+)巨噬细胞中的细胞内源性表达是调节抗埃博拉病毒免疫反应的一个重要因素。CD169(+)巨噬细胞中Usp18的缺失导致VSV-EBOV的局部复制减少，继而导致先天免疫反应和获得性免疫反应减弱。CD169-Cre(+/ki)x Usp18(fl/fl)小鼠对VSV野生型毒株的先天和获得性免疫反应降低，感染后迅速死亡，这表明缺乏Usp18使小鼠更容易受到VSV载体副作用的影响。综上所述，我们的研究表明，Usp18在CD169(+)巨噬细胞中的表达是有效免疫VSV-EBOV的一个重要的替代标志，也可能是其他VSV疫苗的替代标志。
Ebola virus epidemics can be effectively limited by the VSV-EBOV vaccine (Ervebo) due to its rapid protection abilities; however, side effects prevent the broad use of VSV-EBOV as vaccine. Mechanisms explaining the efficient immune activation after single injection with the VSV-EBOV vaccine remain mainly unknown. Here, using the clinically available VSV-EBOV vaccine (Ervebo), we show that the cell-intrinsic expression of the interferon-inhibitor Usp18 in CD169(+) macrophages is one important factor modulating the anti-Ebola virus immune response. The absence of Usp18 in CD169(+) macrophages led to the reduced local replication of VSV-EBOV followed by a diminished innate as well as adaptive immune response. In line, CD169-Cre(+/ki) x Usp18(fl/fl) mice showed reduced innate and adaptive immune responses against the VSV wildtype strain and died quickly after infection, suggesting that a lack of Usp18 makes mice more susceptible to the side effects of the VSV vector. In conclusion, our study shows that Usp18 expression in CD169(+) macrophages is one important surrogate marker for effective vaccination against VSV-EBOV, and probably other VSV-based vaccines also.