Role of Toll-like receptors in modulation of cytokine storm signaling in SARS-CoV-2-induced COVID-19


Posted: 2021-10-21 19:00:00
A balanced immune regulation is crucial for recognizing an invading pathogen, its killing and its elimination. TLRs are the key regulators of the innate immune system. It helps in identifying between self and non-self-molecule and eventually eliminates the non-self. Endosomal TLR mainly TLR3, TLR7, TLR8 and membrane bound TLR4 has a role in the induction of cytokine storm. TLR7/8 recognize the ssRNA SARS-COV-2 and when it replicates to dsRNA, it is recognized by TLR3 and drive the TRIF mediated inflammatory signaling like NF-κB, MAPK. Such signaling leads to significant transcription and translation of pro-inflammatory genes in, releasing inflammatory molecules into the systemic circulation, causing an imbalance in the system. So, whenever an imbalance occurs, a surge in the pro-inflammatory mediators observed in the blood, including cytokines like IL-2, IL-4, IL-6, IL-1β, IL-8, IFN-γ, TNF-α. IL-6 and IL-1β are one of the driving factors for bringing the cytokine storm into the systemic circulation, which migrate into the other organs, causing multiple organ failure leading to death of the individual with severe illness. This article is protected by copyright. All rights reserved. Keywords: COVID-19; SARS-COV-2; TLRs; cytokines; multiple-organ failure; ssRNA.

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