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Pathogenesis of Sepsis

  • Tjitske S. R. van Engelen
  • W. Joost Wiersinga
  • Tom van der Poll
Chapter

Abstract

Sepsis is a life-threatening organ dysfunction due to a dysregulated host response to infection. Both hyperinflammation and immune suppression ensue, to an extent that is harmful to the host. The inflammatory balance is disturbed, and this is associated with a failure to return to homeostasis.

All pathogens with sufficient load and virulence can cause sepsis, after they succeed to adhere and pass the mucosal barrier of the host. The host defense system can recognize molecular components of invading pathogens, called pathogen-associated molecular patterns (PAMPs), with specialized receptors known as pattern recognition receptors (PRRs). Through several signaling pathways, overstimulation of PRRs has proinflammatory and immune suppressive consequences. Hyperinflammation is characterized by activation of target genes coding for proinflammatory cytokines (leukocyte activation), inefficient use of the complement system, activation of the coagulation system, and concurrent downregulation of anticoagulant mechanisms and necrotic cell death. The release of endogenous molecules by injured cells, called danger-associated molecular patterns (DAMPs) or alarmins, leads to deterioration in a vicious cycle by further stimulation of PRRs. Features of immune suppression are massive apoptosis and thereby depletion of immune cells, reprogramming of monocytes and macrophages to a state of a decreased capacity to release proinflammatory cytokines and a disturbed balance in cellular metabolic processes.

Keywords

Sepsis Pathogenesis Hyperinflammation Immune suppression Pathogen Host response Microbiome 

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Tjitske S. R. van Engelen
    • 1
  • W. Joost Wiersinga
    • 1
    • 2
  • Tom van der Poll
    • 1
    • 2
  1. 1.Center for Experimental Molecular Medicine, Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands
  2. 2.Division of Infectious Diseases, Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands

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