Image_4_Defining the Innate Immune Responses for SARS-CoV-2-Human Macrophage Interactions.jpeg
Host innate immune response follows severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and it is the driver of the acute respiratory distress syndrome (ARDS) amongst other inflammatory end-organ morbidities. Such life-threatening coronavirus disease 2019 (COVID-19) is heralded by virus-induced activation of mononuclear phagocytes (MPs; monocytes, macrophages, and dendritic cells). MPs play substantial roles in aberrant immune secretory activities affecting profound systemic inflammation and end-organ malfunctions. All follow the presence of persistent viral components and virions without evidence of viral replication. To elucidate SARS-CoV-2-MP interactions we investigated transcriptomic and proteomic profiles of human monocyte-derived macrophages. While expression of the SARS-CoV-2 receptor, the angiotensin-converting enzyme 2, paralleled monocyte-macrophage differentiation, it failed to affect productive viral infection. In contrast, simple macrophage viral exposure led to robust pro-inflammatory cytokine and chemokine expression but attenuated type I interferon (IFN) activity. Both paralleled dysregulation of innate immune signaling pathways, specifically those linked to IFN. We conclude that the SARS-CoV-2-infected host mounts a robust innate immune response characterized by a pro-inflammatory storm heralding end-organ tissue damage.
History
References
- https://doi.org//10.1016/S0140-6736%2820%2930251-8
- https://doi.org//10.1007/s10238-020-00648-x
- https://doi.org//10.1007/s00134-020-05991-x
- https://doi.org//10.1056/NEJMoa2002032
- https://doi.org//10.3389/fmed.2020.594495
- https://doi.org//10.1128/JVI.00127-20
- https://doi.org//10.3389/fimmu.2019.01443
- https://doi.org//10.3390/ijms19092821
- https://doi.org//10.1016/j.coviro.2011.10.026
- https://doi.org//10.1016/S0140-6736%2820%2930183-5
- https://doi.org//10.1080/22221751.2020.1747363
- https://doi.org//10.1101/2020.03.27.20045427
- https://doi.org//10.1016/S2213-2600%2820%2930076-X
- https://doi.org//10.1038/s41577-020-0331-4
- https://doi.org//10.1038/s41467-021-22781-1
- https://doi.org//10.1093/infdis/jiaa356
- https://doi.org//10.1093/infdis/jiaa753
- https://doi.org//10.1016/0022-1759%2894%2990033-7
- https://doi.org//10.1002/cpmc.105
- https://doi.org//10.1016/S0092-8674%2800%2981289-1
- https://doi.org//10.1016/j.biomaterials.2019.119669
- https://doi.org//10.1038/nprot.2008.211
- https://doi.org//10.12688/f1000research.4431.2
- https://doi.org//10.1093/nar/gky1131
- https://doi.org//10.1128/jvi.37.2.755-758.1981
- https://doi.org//10.1073/pnas.58.3.1004
- https://doi.org//10.1186/s12977-014-0133-5
- https://doi.org//10.1113/JP280176
- https://doi.org//10.1111/j.2517-6161.1995.tb02031.x
- https://doi.org//10.1093/bioinformatics/btp101
- https://doi.org//10.1161/CIRCULATIONAHA.104.510461
- https://doi.org//10.1042/CS20201511
- https://doi.org//10.1152/ajprenal.90488.2008
- https://doi.org//10.1128/mSphereDirect.00120-18
- https://doi.org//10.1073/pnas.93.2.700
- https://doi.org//10.1016/j.tim.2014.12.003
- https://doi.org//10.1111/resp.12657
- https://doi.org//10.1016/j.it.2020.10.012
- https://doi.org//10.1038/s41598-020-75659-5
- https://doi.org//10.1073/pnas.2003138117
- https://doi.org//10.1146/annurev-virology-110615-042301
- https://doi.org//10.1038/nrmicro2147
- https://doi.org//10.4049/jimmunol.1701543
- https://doi.org//10.4049/jimmunol.0904181
- https://doi.org//10.1371/journal.pone.0070308
- https://doi.org//10.15252/embr.202051252
- https://doi.org//10.1161/HYPERTENSIONAHA.114.03743
- https://doi.org//10.1101/2020.09.17.300996
- https://doi.org//10.1016/j.isci.2021.102420
- https://doi.org//10.1074/jbc.M505111200
- https://doi.org//10.1016/j.virusres.2004.09.004
- https://doi.org//10.1093/infdis/jit504
- https://doi.org//10.1007/s00281-017-0629-x
- https://doi.org//10.1038/s41591-020-0901-9
- https://doi.org//10.4049/jimmunol.168.9.4531
- https://doi.org//10.1016/j.jmb.2013.11.024
- https://doi.org//10.1016/j.cell.2019.11.001
- https://doi.org//10.1016/j.isci.2021.102295
- https://doi.org//10.1007/s00251-020-01165-7
- https://doi.org//10.1155/2017/3908061
- https://doi.org//10.1101/gad.1228704
- https://doi.org//10.1074/jbc.M205107200
- https://doi.org//10.1074/jbc.M301789200
- https://doi.org//10.1126/science.1132998
- https://doi.org//10.1007/s12250-016-3726-4
- https://doi.org//10.1016/j.celrep.2020.108234
Usage metrics
Read the peer-reviewed publication
Categories
- Transplantation Immunology
- Tumour Immunology
- Immunology not elsewhere classified
- Immunology
- Veterinary Immunology
- Animal Immunology
- Genetic Immunology
- Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies)
- Autoimmunity
- Cellular Immunology
- Humoural Immunology and Immunochemistry
- Immunogenetics (incl. Genetic Immunology)
- Innate Immunity