The innate immune system acts as the first line of defense against pathogens, including coronaviruses (CoVs). Severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV are epidemic zoonotic CoVs that emerged at the beginning of the 21st century. The recently emerged virus SARS-CoV-2 is a novel strain of CoV that has caused the coronavirus 2019 (COVID-19) pandemic. Scientific advancements made by studying the SARS-CoV and MERS-CoV outbreaks have provided a foundation for understanding pathogenesis and innate immunity against SARS-CoV-2. In this review, we focus on our present understanding of innate immune responses, inflammasome activation, inflammatory cell death pathways, and cytokine secretion during SARS-CoV, MERS-CoV, and SARS-CoV-2 infection. We also discuss how the pathogenesis of these viruses influences these biological processes. Highlights Toll-like receptor (TLR)- and retinoic acid-inducible gene I-like receptor (RLR)-mediated type I interferon (IFN) production is essential for providing protection against coronavirus (CoV) infection; the timing of the IFN response relative to CoV replication determines infection outcomes. Optimal NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation is beneficial for the host but aberrant activation may lead to detrimental CoV infection outcomes. Specific CoV infections can activate inflammatory cell death (PANoptosis), thereby inducing cytokine release. CoV disease tolerance occurs in age-, species-, and sex-dependent manners. More studies are needed to define the innate immune response, specifically during severe acute respiratory syndrome (SARS)-CoV-2 (SARS-CoV-2) infection, and to inform the development of candidate therapeutics.
【저자키워드】 COVID-19, SARS-CoV-2, Inflammation, coronavirus, Cytokines, SARS-CoV, Innate immunity, MERS-CoV, Inflammasome, RNA virus, cell death, MHV, PANoptosis, PANoptosome,