Induction of Innate Immune Response by TLR3 Agonist Protects Mice against SARS-CoV-2 Infection.
Hadas TamirSharon MelamedNoam ErezBoaz PolitiYfat Yahalom-RonenHagit AchdoutShlomi LazarHila GutmanRoy AvrahamShay WeissNir ParanTomer IsraelyPublished in: Viruses (2022)
SARS-CoV-2, a member of the coronavirus family, is the causative agent of the COVID-19 pandemic. Currently, there is still an urgent need in developing an efficient therapeutic intervention. In this study, we aimed at evaluating the therapeutic effect of a single intranasal treatment of the TLR3/MDA5 synthetic agonist Poly(I:C) against a lethal dose of SARS-CoV-2 in K18-hACE2 transgenic mice. We demonstrate here that early Poly(I:C) treatment acts synergistically with SARS-CoV-2 to induce an intense, immediate and transient upregulation of innate immunity-related genes in lungs. This effect is accompanied by viral load reduction, lung and brain cytokine storms prevention and increased levels of macrophages and NK cells, resulting in 83% mice survival, concomitantly with long-term immunization. Thus, priming the lung innate immunity by Poly(I:C) or alike may provide an immediate, efficient and safe protective measure against SARS-CoV-2 infection.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- inflammatory response
- toll like receptor
- immune response
- innate immune
- randomized controlled trial
- nk cells
- signaling pathway
- adipose tissue
- metabolic syndrome
- white matter
- blood brain barrier
- wild type
- functional connectivity
- cell death
- pi k akt
- subarachnoid hemorrhage
- cell cycle arrest