Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Department of Histopathology, Aarhus University Hospital, Aarhus, Denmark.
Life Sci Alliance. 2023 Jun 5;6(8). doi: 10.26508/lsa.202301997. Print 2023 Aug.
Critical COVID-19 is characterized by lack of early type I interferon-mediated host defense and subsequent hyper-inflammation in the lungs. Aberrant activation of macrophages and neutrophils has been reported to lead to excessive activation of innate immunological pathways. It has recently been suggested that the DNA-sensing cGAS-STING pathway drives pathology in the SARS-CoV-2-infected lungs, but mechanistic understanding from in vivo models is needed. Here, we tested whether STING is involved in COVID-19-like disease using the K18-hACE2 mouse model. We report that disease development after SARS-CoV-2 infection is unaltered in STING-deficient K18-hACE2 mice. In agreement with this, STING deficiency did not affect control of viral replication or production of interferons and inflammatory cytokines. This was accompanied by comparable profiles of infiltrating immune cells into the lungs of infected mice. These data do not support a role for STING in COVID-19 pathology and calls for further investigation into the pathogenesis of critical COVID-19.
严重的 COVID-19 的特征是缺乏早期 I 型干扰素介导的宿主防御，随后肺部发生过度炎症。据报道，巨噬细胞和中性粒细胞的异常激活会导致先天免疫途径的过度激活。最近有人提出，DNA 感应 cGAS-STING 途径驱动 SARS-CoV-2 感染肺部的病理，但需要来自体内模型的机制理解。在这里，我们使用 K18-hACE2 小鼠模型测试了 STING 是否参与 COVID-19 样疾病。我们报告说，在 STING 缺陷型 K18-hACE2 小鼠中，SARS-CoV-2 感染后的疾病发展没有改变。与此一致的是，STING 缺陷不影响病毒复制的控制或干扰素和炎症细胞因子的产生。这伴随着感染小鼠肺部浸润免疫细胞的相似谱。这些数据不支持 STING 在 COVID-19 病理中的作用，并呼吁进一步研究严重 COVID-19 的发病机制。
