An article published in the Physiological Genomics (American physiological society) suggests immunomodulation through activation of the innate immune sensor toll-like receptor 5 (TLR5) as an innovative approach to fight COVID-19.

TLR5 is an extracellular pattern recognition receptor that recognizes flagellin, a structural protein of flagellum found in motile Gram-positive and Gram-negative bacteria

The authors hypothesize that flagellin could act as a trojan horse “danger” signal, which favorably tricks” the host into thinking that immune responses are required to subdue a “bacterial” infection but instead triggers antiviral responses to strike SARS-CoV-2

The authors also report that flagellin also elicited NLR family CARD domain containing 4 (NLRC4)-dependent IL-18 production to promote RV clearance

Innate immunity may be the key to defeat severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In the early stage of infection, coronaviruses are capable of inhibiting host type I interferon (IFN) antiviral immune defenses. We propose to counteract this by utilizing flagellin to activate Toll-like receptor 5 (TLR5). TLR5 can induce the production of cytokines (i.e., IL-22, IL-18) and IFN-β, which may restore the impaired immune responses. In the late stage of infection, there is a proinflammatory cytokine storm initiated by innate immune cells like neutrophils (NEU). Theoretically, this can result in inappropriate levels of neutrophil extracellular traps (NETs) and reactive oxygen species (ROS) that cause unwarranted collateral damage. Deoxyribonuclease I (DNase I)-mediated degradation of NETs could provide a therapeutic avenue to suppress excess injury.

https://doi.org/10.1152/physiolgenomics.00033.2020

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Related: https://www.nature.com/articles/s41586-019-1593-5

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