The cellular basis of organ failure in sepsis-signaling during damage and repair processes.

Abstract

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. This definition, updated in 2016, shifted the conceptual focus from exclusive attention to the systemic inflammatory response toward the multifactorial tissue damage that occurs during the progression of infection to sepsis and shock. Whereas targeting the inflammatory host response to infection did not translate into improved clinical management of sepsis, recent findings might shed new light on the maladaptive host-pathogen interaction in sepsis and pave the way for "theranostic" interventions. In addition to the well-known resistance responses of the immune system that result in pathogen clearance, "disease tolerance" has recently been acknowledged as a coping mechanism of presumably equal importance. We propose that both defense mechanisms, "resistance" and "disease tolerance", can get out of control in sepsis. Whereas excessive activation of resistance pathways propagates tissue damage via immunopathology, an inappropriate "tolerance" might entail immunoparalysis accompanied by fulminant, recurrent or persisting infection. The review introduces key signaling processes involved in infection-induced "resistance" and "tolerance". We propose that elaboration of these signaling pathways allows novel insights into sepsis-associated tissue damage and repair processes. Moreover theranostic opportunities for the specific treatment of sepsis-related hyperinflammation or immunoparalysis will be introduced. Agents specifically affecting either hyperinflammation or immunoparalysis in the course of sepsis might add to the therapeutic toolbox of personalized care in the field of organ dysfunction caused by infection. (This article is freely available.).

• Authors: M Bauer, R Wetzker
• Journal: Medizinische Klinik, Intensivmedizin und Notfallmedizin (Med Klin Intensivmed Notfmed) Vol. 115 Issue Suppl 1 Pg. 4-9 (May 2020) ISSN: 2193-6226 [Electronic] Germany
• Vernacular Title: Die zelluläre Basis des Organversagens bei Sepsis – Signalwege in Gewebeschädigung und Reparaturprozessen.
• PMID: 32236799 (Publication Type: Journal Article, Review)

Topics

• Bacterial Infections
• Humans
• Sepsis (therapy)
• Signal Transduction