Caspase-4/11 exacerbates disease severity in SARS–CoV-2 infection by promoting inflammation and immunothrombosis-Reference-Cited by-同舟云学术

Caspase-4/11 exacerbates disease severity in SARS–CoV-2 infection by promoting inflammation and immunothrombosis

Published:2022-05-19 Issue:21 Volume:119 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Eltobgy Mostafa M.¹²³^ORCID,Zani Ashley¹³,Kenney Adam D.¹³,Estfanous Shady¹³⁴,Kim Eunsoo³⁵^ORCID,Badr Asmaa¹³,Carafice Cierra¹³,Daily Kylene¹³^ORCID,Whitham Owen¹³,Pietrzak Maciej⁶,Webb Amy⁶,Kawahara Jeffrey¹³^ORCID,Eddy Adrian C.¹³,Denz Parker¹³^ORCID,Lu Mijia³⁵^ORCID,KC Mahesh³⁷^ORCID,Peeples Mark E.³⁷,Li Jianrong³⁵,Zhu Jian³⁸,Que Jianwen⁹^ORCID,Robinson Richard¹³^ORCID,Rosas Mejia Oscar¹³^ORCID,Rayner Rachael E.³⁵^ORCID,Hall-Stoodley Luanne¹³^ORCID,Seveau Stephanie¹³,Gavrilin Mikhail A.³,Zhang Xiaoli⁶,Thomas Jeronay¹⁰^ORCID,Kohlmeier Jacob E.¹⁰,Suthar Mehul S.¹⁰¹¹¹²^ORCID,Oltz Eugene¹^ORCID,Tedeschi Andrea¹³,Robledo-Avila Frank H.¹⁴^ORCID,Partida-Sanchez Santiago¹⁴^ORCID,Hemann Emily A.¹³,Abdelrazik Eman¹⁵^ORCID,Forero Adriana¹³,Nimjee Shahid M.¹⁶^ORCID,Boyaka Prosper N.³⁵^ORCID,Cormet-Boyaka Estelle³⁵,Yount Jacob S.¹³,Amer Amal O.¹³^ORCID

Affiliation:

1. Department of Microbial Infection and Immunity, The Ohio State University College of Medicine, Columbus, OH 43210

2. Neuroscience graduate program, The Ohio State University, Columbus, OH 43210

3. Infectious Diseases Institute, The Ohio State University, Columbus, OH 43210

4. Faculty of Pharmacy, Helwan University, Cairo,11731 Egypt

5. Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210

6. Department of Biomedical Informatics, The Ohio State University, Columbus, OH 43210

7. Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205

8. Department of Pathology, The Ohio State University, Columbus, OH 43210

9. Division of Digestive and Liver Diseases and Center for Human Development, Department of Medicine, Columbia University, New York, NY 10027

10. Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322

11. Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322

12. Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322

13. Department of Neuroscience, Chronic Brain Injury Discovery Theme, The Ohio State University, Columbus, OH 43210

14. Center for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205

15. Center for Informatics Science, Nile University, Giza, 12525, Egypt

16. Department of Neurological Surgery, The Ohio State University, Columbus, OH 43210

Abstract

Significance We report the discovery of fundamental roles for the noncanonical inflammasome molecule Caspase-4/11 in promoting pathological inflammatory and prothrombotic pathways in severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2) infections. Our work demonstrates that Caspase-11 has a broader role in immune responses beyond its previously appreciated effects in bacterial infections. Further, we show that Caspase-11–deficient mice infected with SARS–CoV-2 fare significantly better in terms of overall illness, lung inflammation, and thrombosis than wild-type (WT) mice, thus implicating Caspase-11 as a new therapeutic target for preventing or treating COVID-19.

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Link

https://pnas.org/doi/pdf/10.1073/pnas.2202012119

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