RNASE L MEDIATES THE TLR4 SIGNALING PATHWAY

Abstract

RNase L is an important enzyme that has a critical role in the IFN antiviral function and the control of cell proliferation. Also, RNase L is engaged in various biological processes such as gene expression control, cell death, and innate immunity. RNase L is present in large concentrations in the thymus, spleen, and most immune cells such as T, B, and macrophages, showing that RNase L plays a role in the immune system. The Toll-Like Receptor 4 (TLR 4) is a specific recognition receptor for endotoxins such as lipopolysaccharide (LPS), viruses, fungi, and other microbiological substances. Upon the binding of these ligands on the receptor, the TLR4 signaling pathway is activated, leading to inflammatory cytokine release which is responsible for initiating the innate immune system. However, a definite connection between RNase L and the TLR4 signaling pathway still needs to be investigated. Here, we discovered that the RNase L is involved in the TLR4 signaling pathway in viral and bacterial infections. Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the coronavirus 2 and is associated with severe acute respiratory syndrome. The severity and consequences of this disease are determined by the amount of inflammatory response in the body. The SARS-CoV-2 spike protein S1 subunit induces pro-inflammatory responses in macrophages via interaction with toll-like receptor 4 (TLR 4) and human angiotensin-converting enzyme 2 (ACE 2). The physiological significance of RNase L in Coronavirus illness, on the other hand, remains unknown. We discovered that RNase L affects the TLR4 signaling pathway in macrophages upon stimulation with the spike protein S1 subunit. Additionally, we discovered that the presence of RNase L activates the TLR4 signaling pathway in a variety of cell lines treated with LPS (bacterial infection). The involvement of RNase L in these microbial infections may or may not be due to its endonuclease activity. These findings suggest that RNase L has a novel function in the immune response to bacterial and viral inflammation.