Stegeman Sophia K, Kourko Olena, Amsden Heather, Pellizzari Delano Isabella E, Mamatis John E, Roth Madison, Colpitts Che C, Gee Katrina
Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
J Innate Immun. 2025;17(1):126-153. doi: 10.1159/000543608. Epub 2025 Jan 16.
The interactions between viruses and the host immune response are nuanced and intricate. The cytokine response arguably plays a central role in dictating the outcome of virus infection, balancing inflammation, and healing, which is crucial to resolving infection without destructive immunopathologies.
Early innate immune responses are key to the generation of a beneficial or detrimental immune response. These initial responses are regulated by a plethora of surface bound, endosomal, and cytoplasmic innate immune receptors known as pattern recognition receptors. Of these, the Toll-like receptors (TLRs) play an important role in the induction of cytokines during virus infection. Recognizing pathogen-associated molecular patterns (PAMPs) such as viral proteins and/or nucleotide sequences, the TLRs act as sentinels for the initiation and propagation of immune responses.
TLRs are important receptors for initiating the innate response to single-stranded RNA (ssRNA) viruses like influenza A virus (IAV), severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1), SARS-CoV-2, Middle East respiratory syndrome coronavirus, dengue virus, and Ebola virus. Infection with these viruses is also associated with aberrant expression of proinflammatory cytokines that contribute to a harmful cytokine storm response. Herein we discuss the connections between these ssRNA viruses, cytokine storm, and the roles of TLRs.
The interactions between viruses and the host immune response are nuanced and intricate. The cytokine response arguably plays a central role in dictating the outcome of virus infection, balancing inflammation, and healing, which is crucial to resolving infection without destructive immunopathologies.
Early innate immune responses are key to the generation of a beneficial or detrimental immune response. These initial responses are regulated by a plethora of surface bound, endosomal, and cytoplasmic innate immune receptors known as pattern recognition receptors. Of these, the Toll-like receptors (TLRs) play an important role in the induction of cytokines during virus infection. Recognizing pathogen-associated molecular patterns (PAMPs) such as viral proteins and/or nucleotide sequences, the TLRs act as sentinels for the initiation and propagation of immune responses.
TLRs are important receptors for initiating the innate response to single-stranded RNA (ssRNA) viruses like influenza A virus (IAV), severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1), SARS-CoV-2, Middle East respiratory syndrome coronavirus, dengue virus, and Ebola virus. Infection with these viruses is also associated with aberrant expression of proinflammatory cytokines that contribute to a harmful cytokine storm response. Herein we discuss the connections between these ssRNA viruses, cytokine storm, and the roles of TLRs.
病毒与宿主免疫反应之间的相互作用微妙而复杂。细胞因子反应在决定病毒感染的结果、平衡炎症和愈合方面 arguably 起着核心作用，这对于在无破坏性免疫病理的情况下解决感染至关重要。
早期先天免疫反应是产生有益或有害免疫反应的关键。这些初始反应由大量表面结合、内体和细胞质的先天免疫受体调节，这些受体被称为模式识别受体。其中，Toll 样受体（TLRs）在病毒感染期间细胞因子的诱导中起重要作用。TLRs 通过识别病原体相关分子模式（PAMPs），如病毒蛋白和/或核苷酸序列，充当免疫反应启动和传播的哨兵。
TLRs 是启动对甲型流感病毒（IAV）、严重急性呼吸综合征冠状病毒 1（SARS-CoV-1）、SARS-CoV-2、中东呼吸综合征冠状病毒、登革热病毒和埃博拉病毒等单链 RNA（ssRNA）病毒的先天反应的重要受体。感染这些病毒还与促炎细胞因子的异常表达有关，这会导致有害的细胞因子风暴反应。在此，我们讨论这些 ssRNA 病毒、细胞因子风暴和 TLRs 的作用之间的联系。
病毒与宿主免疫反应之间的相互作用微妙而复杂。细胞因子反应在决定病毒感染的结果、平衡炎症和愈合方面 arguably 起着核心作用，这对于在无破坏性免疫病理的情况下解决感染至关重要。
早期先天免疫反应是产生有益或有害免疫反应的关键。这些初始反应由大量表面结合、内体和细胞质的先天免疫受体调节，这些受体被称为模式识别受体。其中，Toll 样受体（TLRs）在病毒感染期间细胞因子的诱导中起重要作用。TLRs 通过识别病原体相关分子模式（PAMPs），如病毒蛋白和/或核苷酸序列，充当免疫反应启动和传播的哨兵。
TLRs 是启动对甲型流感病毒（IAV）、严重急性呼吸综合征冠状病毒 1（SARS-CoV-1）SARS-CoV-2、中东呼吸综合征冠状病毒、登革热病毒和埃博拉病毒等单链 RNA（ssRNA）病毒的先天反应的重要受体。感染这些病毒还与促炎细胞因子的异常表达有关，这会导致有害的细胞因子风暴反应。在此，我们讨论这些 ssRNA 病毒、细胞因子风暴和 TLRs 的作用之间的联系。
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