@article{95e17ce14f9541b2914a09604e8fe4c8,
title = "Synergism of TNF-α and IFN-γ Triggers Inflammatory Cell Death, Tissue Damage, and Mortality in SARS-CoV-2 Infection and Cytokine Shock Syndromes",
abstract = "TNF-α and IFN-γ synergize to drive the cytokine storm and cell death associated with COVID-19 and sepsis.",
keywords = "COVID-19, IFN-γ, PANoptosis, SARS-CoV-2, TNF-α, apoptosis, cytokine storm, inflammation, necroptosis, pyroptosis",
author = "Rajendra Karki and Sharma, {Bhesh Raj} and Shraddha Tuladhar and Williams, {Evan Peter} and Lillian Zalduondo and Parimal Samir and Min Zheng and Balamurugan Sundaram and Balaji Banoth and Malireddi, {R. K.Subbarao} and Patrick Schreiner and Geoffrey Neale and Peter Vogel and Richard Webby and Jonsson, {Colleen Beth} and Kanneganti, {Thirumala Devi}",
note = "Funding Information: We thank all the members of the Kanneganti laboratory for their comments and suggestions during the development of this manuscript. We thank A. Burton (St. Jude Children{\textquoteright}s Research Hospital) for her technical support. We also thank R. Tweedell, PhD, for scientific editing and writing support. Work from our laboratory is supported by the US National Institutes of Health ( AI101935 , AI124346 , AR056296 , and CA253095 to T.-D.K.) and the American Lebanese Syrian Associated Charities (to T.-D.K.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The Irf3 −/− , Irf7 −/− , and Irf9 −/− mutant mice were provided by RIKEN BRC through the National Bio-Resource Project of the MEXT, Japan. We thank V.M. Dixit and N. Kayagaki (Genentech) for the Casp11 −/− and Casp1 −/− Casp11 −/− mutant mouse strains. We thank Dr. Michael Gale for the Mavs −/− mutant mouse strain. We thank K. Pfeffer for the Gbp2 –/– mutant mouse strain. The following reagent was deposited by the Centers for Disease Control and Prevention and obtained through BEI Resources, NIAID, NIH: SARS-Related Coronavirus 2, Isolate USA-WA1/2020, NR-52281. The graphical abstract was created using BioRender. Funding Information: We thank all the members of the Kanneganti laboratory for their comments and suggestions during the development of this manuscript. We thank A. Burton (St. Jude Children's Research Hospital) for her technical support. We also thank R. Tweedell, PhD, for scientific editing and writing support. Work from our laboratory is supported by the US National Institutes of Health (AI101935, AI124346, AR056296, and CA253095 to T.-D.K.) and the American Lebanese Syrian Associated Charities (to T.-D.K.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The Irf3?/?, Irf7?/?, and Irf9?/? mutant mice were provided by RIKEN BRC through the National Bio-Resource Project of the MEXT, Japan. We thank V.M. Dixit and N. Kayagaki (Genentech) for the Casp11?/? and Casp1?/?Casp11?/? mutant mouse strains. We thank Dr. Michael Gale for the Mavs?/? mutant mouse strain. We thank K. Pfeffer for the Gbp2?/? mutant mouse strain. The following reagent was deposited by the Centers for Disease Control and Prevention and obtained through BEI Resources, NIAID, NIH: SARS-Related Coronavirus 2, Isolate USA-WA1/2020, NR-52281. The graphical abstract was created using BioRender. R.K. and T.-D.K. conceptualized the study; R.K. and B.R.S. designed the methodology; R.K. B.R.S. S.T. E.P.W. L.Z. M.Z. B.S. B.B. and R.K.S.M. performed the experiments; P. Samir, P. Schreiner, and G.N. conducted the gene expression and publicly available dataset analysis; C.B.J. and R.W. directed the SARS-CoV-2 infections and provided scientific discussion; P.V. conducted the immunohistochemistry and pathology analysis; R.K. and T.-D.K. wrote the manuscript with input from all the authors. T.-D.K. acquired the funding and provided overall supervision. St. Jude Children's Research hospital filed a provisional patent application on TNF-? and IFN-? signaling described in this study, listing R.K. and T.-D.K. as inventors (serial no. 63/106,012). Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2021",
month = jan,
day = "7",
doi = "10.1016/j.cell.2020.11.025",
language = "English (US)",
volume = "184",
pages = "149--168.e17",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "1",
}