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Innate Recognition and Signaling during Times of Pandemic and Beyond from Intensive Care Perspective

The systemic inflammatory response (SIRS) underlies the majority of intensive care-related conditions. Depending on the origin it may become a governing force of organ dysfunctions. The immune response therefore may be a contemptuous reaction. While necessary for viral, or bacterial elimination, clearance of debris, and regeneration, when dysregulated, overpowering, or chronically ongoing, it may lead to significant collateral damage, organ failure, and autoimmunity. Understanding the immune response in specific complex situations, monitoring, and targeted influencing may become a future step in intensive care management. Toll-like receptor four (TLR4) is a representative innate immune receptor with authoritative downstream signaling and regulatory functions. The following review aims to bridge the logics of innate immune recognition, signaling, and influence on intensive care-related acute conditions by TLR4. We demonstrate that overwhelming innate immune response can be blunted, skewed, and consequently, adaptive immunity positively influenced, but such an approach must be careful and targeted for specific situations optimally under comprehensive immune monitoring. The unanswered questions of the field, as well as possible caveats of such novel approaches, are mapped through discussing in vitro and animal models, human trials. Review Article Frisancho-Kiss; JAMMR, 33(12): 130-143, 2021; Article no.JAMMR.68474 131