Inflammasome regulation in driving COVID‐19 severity in humans and immune tolerance in bats

Autor: Disha Jain, Sannula Kesavardhana, Sahana Nagaraja
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Journal of Leukocyte Biology
ISSN: 1938-3673
0741-5400
Popis: Coronaviruses (CoVs) are RNA viruses that cause human respiratory infections. Zoonotic transmission of the SARS‐CoV‐2 virus caused the recent COVID‐19 pandemic, which led to over 2 million deaths worldwide. Elevated inflammatory responses and cytotoxicity in the lungs are associated with COVID‐19 severity in SARS‐CoV‐2‐infected individuals. Bats, which host pathogenic CoVs, operate dampened inflammatory responses and show tolerance to these viruses with mild clinical symptoms. Delineating the mechanisms governing these host‐specific inflammatory responses is essential to understand host–virus interactions determining the outcome of pathogenic CoV infections. Here, we describe the essential role of inflammasome activation in determining COVID‐19 severity in humans and innate immune tolerance in bats that host several pathogenic CoVs. We further discuss mechanisms leading to inflammasome activation in human SARS‐CoV‐2 infection and how bats are molecularly adapted to suppress these inflammasome responses. We also report an analysis of functionally important residues of inflammasome components that provide new clues of bat strategies to suppress inflammasome signaling and innate immune responses. As spillover of bat viruses may cause the emergence of new human disease outbreaks, the inflammasome regulation in bats and humans likely provides specific strategies to combat the pathogenic CoV infections.
Graphical Abstract Human SARS‐CoV‐2 infection‐induced inflammasome activation is associated with COVID‐19 severity, whereas bats, which host pathogenic CoVs, show dampened inflammasome activation and immune tolerance to viral infections.
Databáze: OpenAIRE