Deterioration of Organ Function As a Hallmark in Sepsis: The Cellular Perspective

Frontiers in Immunology
Michael BauerReinhard Wetzker

Abstract

Development of organ dysfunction discriminates sepsis from uncomplicated infection. The paradigm shift implicated by the new sepsis-3 definition holds that initial impairment of any organ can pave the way for multiple organ dysfunction and death. Moreover, the role of the systemic inflammatory response, central element in previous sepsis definitions, has been questioned. Most strikingly, a so far largely underestimated defense mechanism of the host, i.e., "disease tolerance," which aims at maintaining host vitality without reducing pathogen load, has gained increasing attention. Here, we summarize evidence that a dysregulation of critical cellular signaling events, also in non-immune cells, might provide a conceptual framework for sepsis-induced dysfunction of parenchymal organs in the absence of significant cell death. We suggest that key signaling mediators, such as phosphoinositide 3-kinase, mechanistic target of rapamycin, and AMP-activated protein kinase, control the balance of damage and repair processes and thus determine the fate of affected organs and ultimately the host. Therapeutic targeting of these multifunctional signaling mediators requires cell-, tissue-, or organ-specific approaches. These novel strategies migh...Continue Reading

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Citations

Mar 17, 2020·EMBO Molecular Medicine·Jean-Marc CavaillonTomasz Skirecki
Apr 3, 2020·Medizinische Klinik, Intensivmedizin und Notfallmedizin·M Bauer, R Wetzker
Apr 24, 2021·Proceedings of the National Academy of Sciences of the United States of America·Woon Yong KwonCarl J Hauser
Jun 4, 2021·Critical Care Explorations·Anuradha RamojiUte Neugebauer
Aug 8, 2021·International Journal of Molecular Sciences·Michael G AppiahMotomu Shimaoka
Dec 30, 2021·Intensive Care Medicine Experimental·Michael BauerReinhard Wetzker

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