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This Special Issue 2.0 continues the conceptional line started in the previous Special Issue, focusing on the involvement of Toll-like receptors (TLRs) and their related signaling pathways in viral infection and inflammation, and emphasizing the therapeutic potential of TLR system modulation for the treatment of acute viral infections and their long-term sequelae and to provide potential targets for treating chronic viral and inflammatory diseases. This Special Issue provides an excellent collection of contemporary reviews and research articles covering a broad variety of topics, ranging from the protective activity of TLRs in viral infections to detrimental disturbances of the host immune system. The most intriguing theme discussed in this second Special Issue is the intercorrelation between acute viral infections and triggered delayed effects, including neuroinflammatory and neurodegenerative long-term sequelae. Notably, new data increasingly show that neurological pathways, such as neurogenesis, neuroinflammation, and cognitive and behavioural aspects, may be influenced by innate, TLR-mediated pathways. In this context, the connection between infection-triggered acute disbalance in TLR activation and resulting neurological sequelae following bacterial (sepsis) or viral infections, including long COVID-associated neurological sequelae, may provide new targets for future treatment options.

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