Fig. 2

Host immune response to coronaviruses (CoVs): a schematic overview. Upon entry into the respiratory epithelium (1), CoV S protein binds to epithelial cells through the entry receptor, promoting viral uptake within the endosome (2). SARS-CoV-1, MERS-CoV, and SARS-CoV-2 are all sensed by the endosomal single-stranded (ss) RNA sensor TLR7; within the cytosol, MERS-CoV is detected by the cytosolic double-stranded (ds) RNA sensor MDA-5. The intracellular sensors respectively recruit the adaptor proteins MyD88 and MAVS and signal (3) for the activation of NF-κB and phosphorylation of IRF3/7 transcription factors (4). This results in the production of proinflammatory cytokines (e.g. IL-6 and TNF-α) and type I IFNs (IFN-α and IFN-β) (5). Type I IFNs recruit and stimulate immune cells, such as alveolar macrophages and lung-residing dendritic cells, to trigger innate and adaptive immune responses. Dendritic cells capture and process the viral antigen for presentation by MHC molecules to T cells. Clonally-expanded specific CD8⁺ T cells assist in clearing the infected cell, recognizing the viral peptide on MHC I (6/7). DC dendritic cell, TLR Toll-like receptor, MDA-5 melanoma differentiation-associated protein 5, MyD88 myeloid differentiation primary response 88, MAVS mitochondrial antiviral-signaling protein, NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells, IRF interferon regulatory factor, TNF tumor necrosis factor, IFN interferon, MHC major histocompatibility complex. Created with BioRender.com