Ectromelia virus (ECTV), an orthopoxvirus, undergoes productive replication in conventional dendritic cells (cDCs), resulting in the inhibition of their innate and adaptive immune functions. ECTV replication rate in cDCs is increased due to downregulation of the expression of cathepsins - cystein proteases that orchestrate several steps during DC maturation. Therefore, this study was aimed to determine if downregulation of cathepsins, such as B, L or S, disrupts cDC capacity to induce activating signals in T cells or whether infection of cDCs with ECTV further weakens their functions as antigen-presenting cells. Our results showed that cDCs treated with siRNA against cathepsin B, L and S synthesize similar amounts of pro-inflammatory cytokines and exhibit comparable ability to mature and stimulate alloreactive CD4+ T cells, as untreated wild type (WT) cells. Moreover, ECTV inhibitory effect on cDC innate and adaptive immune functions, observed especially after LPS treatment, was comparable in both cathepsin-silenced and WT cells. Taken together, the absence of cathepsins B, L and S has minimal, if any, impact on the inhibitory effect of ECTV on cDC immune functions. We assume that the virus-mediated inhibition of cathepsin expression in cDCs represents more a survival mechanism than an immune evasion strategy.

中文翻译：

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所选的组织蛋白酶的缺乏并不影响ECTV对树突状细胞的免疫特性的抑制作用。

痘病毒（正痘病毒）是一种正痘病毒，在常规树突状细胞（cDC）中进行生产性复制，导致其固有免疫功能和适应性免疫功能受到抑制。由于组织蛋白酶-半胱氨酸蛋白酶在DC成熟过程中协调几个步骤的表达下调，因此cDC中ECTV的复制率增加了。因此，本研究旨在确定组织蛋白酶（如B，L或S）的下调是否会破坏cDC诱导T细胞中激活信号的能力，或者用ECTV感染cDC是否进一步削弱了它们作为抗原呈递细胞的功能。我们的结果表明，经siRNA处理的针对组织蛋白酶B，L和S的cDC合成了相似数量的促炎细胞因子，并具有可比的成熟和刺激同种反应性CD4 + T细胞的能力，作为未经处理的野生型（WT）细胞。此外，尤其是在LPS处理后，观察到的ECTV对cDC固有和适应性免疫功能的抑制作用在组织蛋白酶沉默和WT细胞中均相当。总之，组织蛋白酶B，L和S的缺失对ECTV对cDC免疫功能的抑制作用影响很小（如果有的话）。我们假定病毒介导的组织蛋白酶在cDCs中的表达抑制比免疫逃避策略更能代表生存机制。