Division of Immunology, Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - SGGW, Warsaw, Poland.
Department of Food Hygiene and Public Health Protection, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - SGGW, Warsaw, Poland.
Immunol Invest. 2020 Apr;49(3):232-248. doi: 10.1080/08820139.2019.1631843. Epub 2019 Jun 26.
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.
细小病毒（ECTV）是一种正痘病毒，可在常规树突状细胞（cDC）中进行有效复制，从而抑制其固有和适应性免疫功能。由于组织蛋白酶（参与 DC 成熟的几个步骤的半胱氨酸蛋白酶）的表达下调，cDC 中的 ECTV 复制率增加。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 细胞激活信号的能力，或者 ECTV 感染 cDC 是否会进一步削弱它们作为抗原呈递细胞的功能。我们的结果表明，用针对组织蛋白酶 B、L 和 S 的 siRNA 处理的 cDC 合成相似量的促炎细胞因子，并表现出类似的成熟和刺激同种反应性 CD4 T 细胞的能力，与未处理的野生型（WT）细胞相当。此外，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，在沉默 cathepsin 的细胞和 WT 细胞中是相当的。总之，组织蛋白酶 B、L 和 S 的缺失对 ECTV 抑制 cDC 免疫功能的影响最小，如果有的话。我们假设病毒介导的 cDC 中组织蛋白酶表达的抑制更多地代表一种生存机制，而不是免疫逃避策略。
