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Review
. 2017 Oct;1863(10 Pt B):2564-2573.
doi: 10.1016/j.bbadis.2017.01.013. Epub 2017 Jan 20.

Microbial recognition and danger signals in sepsis and trauma

Steven L Raymond  1 , David C Holden  1 , Juan C Mira  1 , Julie A Stortz  1 , Tyler J Loftus  1 , Alicia M Mohr  1 , Lyle L Moldawer  1 , Frederick A Moore  1 , Shawn D Larson  1 , Philip A Efron  2
Affiliations
Review

Microbial recognition and danger signals in sepsis and trauma

Steven L Raymond et al. Biochim Biophys Acta Mol Basis Dis. 2017 Oct.

Abstract

Early host recognition of microbial invasion or damaged host tissues provides an effective warning system by which protective immune and inflammatory processes are initiated. Host tissues responsible for continuous sampling of their local environment employ cell surface and cytosolic pattern recognition receptors (PRRs) that provide redundant and overlapping identification of both microbial and host alarmins. Microbial products containing pathogen-associated molecular patterns (PAMPs), as well as damage-associated molecular patterns (DAMPs) serve as principle ligands for recognition by these PRRs. It is this interaction which plays both an essential survival role in response to infection and injury, as well as the pathologic role in tissue and organ injury associated with severe sepsis and trauma. Elucidating the interaction between ligands and their respective PRRs can provide both a better understanding of the host response, as well as a rational basis for therapeutic intervention. This article is part of a Special Issue entitled: Immune and Metabolic Alterations in Trauma and Sepsis edited by Dr. Raghavan Raju.

Keywords: DAMP; Infection; Inflammation; PAMP; Sepsis; Trauma.

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Figures

Figure 1
Figure 1. TLR receptors and intracellular signaling pathways for the recognition of microbial products and endogenous danger signals
TLR1, 2, 4, 5 and 6 are located on the transmembrane whereas TLR 3, 7, 8 and 9 are located in endosomal vesicles. TLR stimulation allows binding with MyD88, TIRAP, TRAM and TRIF adapter proteins. Downstream signaling occurs via IRAK, TRAF3, TRAF6, TAK1, TBK1 and IKK complexes. Activation of MAPK, NFKB and IRF results in the induction of inflammatory cytokines and type I IFN.
Figure 2
Figure 2. Mechanism of endogenous danger signal release
In response to tissue damage and ischemia, cells actively release HMGB1, Hsps and S100 proteins. Necrotic cells also passively release HMGB1, Hsps proteins, S100 proteins, mitochondrial DNA and nucleic DNA. In contrast, apoptotic cells do not promote inflammation.
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References

    1. Lagu T, et al. Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003 to 2007. Crit Care Med. 2012;40(3):754–761. - PubMed
    1. Centers for Disease Control and Prevention, N.C.f.I.P.a.C. Web-based Injury Statistics Query and Reporting System (WISQRS) 2010
    1. Cudnik MT, et al. Level I versus Level II trauma centers: an outcomes-based assessment. J Trauma. 2009;66(5):1321–1326. - PubMed
    1. Demetriades D, et al. Relationship between American College of Surgeons trauma center designation and mortality in patients with severe trauma (injury severity score > 15) J Am Coll Surg. 2006;202(2):212–215. quiz A45. - PubMed
    1. Levy MM, et al. Surviving Sepsis Campaign: association between performance metrics and outcomes in a 7.5-year study. Crit Care Med. 2015;43(1):3–12. - PubMed

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