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Post by Nadica (She/Her) on Jun 24, 2024 8:29:54 GMT
SARS-CoV-2 envelope protein regulates innate immune tolerance - Published May 15, 2024Highlights •SARS-CoV-2 envelope (E) protein activated innate immune cells through TLR2 •E protein promoted a long-term tolerant immune state after initial activation •Monocytes in this tolerant state had reduced responsiveness to secondary stimuli •E protein priming reduced lung inflammation markers to LPS in neonatal mice Summary Severe COVID-19 often leads to secondary infections and sepsis that contribute to long hospital stays and mortality. However, our understanding of the precise immune mechanisms driving severe complications after SARS-CoV-2 infection remains incompletely understood. Here, we provide evidence that the SARS-CoV-2 envelope (E) protein initiates innate immune inflammation, via toll-like receptor 2 signaling, and establishes a sustained state of innate immune tolerance following initial activation. Monocytes in this tolerant state exhibit reduced responsiveness to secondary stimuli, releasing lower levels of cytokines and chemokines. Mice exposed to E protein before secondary lipopolysaccharide challenge show diminished pro-inflammatory cytokine expression in the lung, indicating that E protein drives this tolerant state in vivo. These findings highlight the potential of the SARS-CoV-2 E protein to induce innate immune tolerance, contributing to long-term immune dysfunction that could lead to susceptibility to subsequent infections, and uncovers therapeutic targets aimed at restoring immune function following SARS-CoV-2 infection. Graphical abstract
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