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Front. Immunol. | doi: 10.3389/fimmu.2018.01460

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

Michael Bauer1, 2*,  Sina M. Coldewey1, 2, 3,  Margit Leitner2, Bettina Löffler2, 4, Sebastian Weis1, 2, 5 and  Reinhard Wetzker1
  • 1Department of Anesthesiology and Intensive Care Medicine, Universitätsklinikum Jena, Germany
  • 2Center for Sepsis Control and Care, Universitätsklinikum Jena, Germany
  • 3Septomics Research Center, Universitätsklinikum Jena, Germany
  • 4Institute of Medical Microbiology, Universitätsklinikum Jena, Germany
  • 5Center for Infectious Disease and Infection Control, Universitätsklinikum Jena, Germany

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 PI3K, mTOR and AMPK, control the balance of damage and repair processes and thus determine the fate of affected organs and ultimately the host. Therapeutic targeting of these multi-functional signaling mediators requires cell-, tissue-, or organ-specific approaches. These novel strategies might allow stopping the domino-like damage to further organ systems and offer alternatives beyond the currently available strictly supportive therapeutic options.

Keywords: Sepsis, Organ dysfunction, metabolic adaptation, disease tolerance, signaling

Received: 18 Dec 2017; Accepted: 12 Jun 2018.

Edited by:

Tobias Schuerholz, Universitätsmedizin Rostock, Germany

Reviewed by:

Dror Mevorach, Hadassah Medical Center, Israel
Markus Bosmann, Boston University, United States
Hugo C. Castro-Faria-Neto, Fundação Oswaldo Cruz (Fiocruz), Brazil  

Copyright: © 2018 Bauer, Coldewey, Leitner, Löffler, Weis and Wetzker. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Michael Bauer, Universitätsklinikum Jena, Department of Anesthesiology and Intensive Care Medicine, Am Klinikum 1, Jena, 07747, Germany, michael.bauer@med.uni-jena.de