Proc Natl Acad Sci U S A . Caspase-4/11 exacerbates disease severity in SARS-CoV-2 infection by promoting inflammation and immunothrombosis

[tetano]

Proc Natl Acad Sci U S A


. 2022 May 24;119(21):e2202012119.
doi: 10.1073/pnas.2202012119. Epub 2022 May 19.
Caspase-4/11 exacerbates disease severity in SARS-CoV-2 infection by promoting inflammation and immunothrombosis


Mostafa M Eltobgy[SUP] 1 2 3 [/SUP], Ashley Zani[SUP] 1 3 [/SUP], Adam D Kenney[SUP] 1 3 [/SUP], Shady Estfanous[SUP] 1 3 4 [/SUP], Eunsoo Kim[SUP] 3 5 [/SUP], Asmaa Badr[SUP] 1 3 [/SUP], Cierra Carafice[SUP] 1 3 [/SUP], Kylene Daily[SUP] 1 3 [/SUP], Owen Whitham[SUP] 1 3 [/SUP], Maciej Pietrzak[SUP] 6 [/SUP], Amy Webb[SUP] 6 [/SUP], Jeffrey Kawahara[SUP] 1 3 [/SUP], Adrian C Eddy[SUP] 1 3 [/SUP], Parker Denz[SUP] 1 3 [/SUP], Mijia Lu[SUP] 3 5 [/SUP], Mahesh Kc[SUP] 3 7 [/SUP], Mark E Peeples[SUP] 3 7 [/SUP], Jianrong Li[SUP] 3 5 [/SUP], Jian Zhu[SUP] 3 8 [/SUP], Jianwen Que[SUP] 9 [/SUP], Richard Robinson[SUP] 1 3 [/SUP], Oscar Rosas Mejia[SUP] 1 3 [/SUP], Rachael E Rayner[SUP] 3 5 [/SUP], Luanne Hall-Stoodley[SUP] 1 3 [/SUP], Stephanie Seveau[SUP] 1 3 [/SUP], Mikhail A Gavrilin[SUP] 3 [/SUP], Xiaoli Zhang[SUP] 6 [/SUP], Jeronay Thomas[SUP] 10 [/SUP], Jacob E Kohlmeier[SUP] 10 [/SUP], Mehul S Suthar[SUP] 10 11 12 [/SUP], Eugene Oltz[SUP] 1 [/SUP], Andrea Tedeschi[SUP] 13 [/SUP], Frank H Robledo-Avila[SUP] 14 [/SUP], Santiago Partida-Sanchez[SUP] 14 [/SUP], Emily A Hemann[SUP] 1 3 [/SUP], Eman Abdelrazik[SUP] 15 [/SUP], Adriana Forero[SUP] 1 3 [/SUP], Shahid M Nimjee[SUP] 16 [/SUP], Prosper N Boyaka[SUP] 3 5 [/SUP], Estelle Cormet-Boyaka[SUP] 3 5 [/SUP], Jacob S Yount[SUP] 1 3 [/SUP], Amal O Amer[SUP] 1 3 [/SUP]



Affiliations

• PMID: 35588457
• DOI: 10.1073/pnas.2202012119

Abstract

SignificanceWe 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.

Keywords: SARS–CoV-2; innate immunity; thrombosis.