Paludan Søren R, Pradeu Thomas, Pichlmair Andreas, Wray K Brad, Mikkelsen Jacob Giehm, Olagnier David, Mogensen Trine H
Department of Biomedicine, Aarhus University, Aarhus, Denmark; Center for Immunology of Viral Infections, Aarhus University, Aarhus, Denmark; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
CNRS UMR 5164 ImmunoConcept, University of Bordeaux, Bordeaux, France; Department of Biological and Medical Sciences, University of Bordeaux, Bordeaux, France; Chapman University, Orange, CA, USA.
Cell Rep. 2024 Dec 24;43(12):115070. doi: 10.1016/j.celrep.2024.115070. Epub 2024 Dec 13.
Early host defense eliminates many viruses before infections are established while clearing others so they remain subclinical or cause only mild disease. The field of immunology has been shaped by broad concepts, including the pattern recognition theory that currently dominates innate immunology. Focusing on early host responses to virus infections, we analyze the literature to build a working hypothesis for the principles that govern the early line of cellular antiviral defense. Aiming to ultimately arrive at a criteria-based theory with strong explanatory power, we propose that both controlling infection and limiting inflammation are key drivers for the early cellular antiviral response. This response, which we suggest is exerted by a set of "microbe- and inflammation-restricting mechanisms," directly restrict viral replication while also counteracting inflammation. Exploring the mechanisms and physiological importance of the early layer of cellular antiviral defense may open further lines of research in immunology.
早期宿主防御在感染确立之前就能清除许多病毒,同时清除其他病毒,使它们保持亚临床状态或仅引起轻微疾病。免疫学领域一直受到广泛概念的影响,包括目前主导先天免疫的模式识别理论。我们聚焦于宿主对病毒感染的早期反应,分析文献以构建一个关于细胞抗病毒防御早期防线调控原则的工作假说。为了最终得出具有强大解释力的基于标准的理论,我们提出控制感染和限制炎症都是细胞抗病毒早期反应的关键驱动因素。我们认为这种反应是由一组“微生物和炎症限制机制”发挥作用的,它们直接限制病毒复制,同时对抗炎症。探索细胞抗病毒防御早期层面的机制和生理重要性可能会开启免疫学的进一步研究方向。