Host Innate Immune Responses to Sepsis

Overview

Journal Virulence

Specialty Microbiology

Date 2013 Jun 19

PMID 23774844

Citations 195

Authors

Willem Joost Wiersinga

Stije J Leopold

Duncan R Cranendonk

Tom van der Poll

Affiliations

Soon will be listed here.

Abstract

The immune response to sepsis can be seen as a pattern recognition receptor-mediated dysregulation of the immune system following pathogen invasion in which a careful balance between inflammatory and anti-inflammatory responses is vital. Invasive infection triggers both pro-inflammatory and anti-inflammatory host responses, the magnitude of which depends on multiple factors, including pathogen virulence, site of infection, host genetics, and comorbidities. Toll-like receptors, the inflammasomes, and other pattern recognition receptors initiate the immune response after recognition of danger signals derived from microorganisms, so-called pathogen-associated molecular patterns or derived from the host, so-called danger-associated molecular patterns. Further dissection of the role of host-pathogen interactions, the cytokine response, the coagulation cascade, and their multidirectional interactions in sepsis should lead toward the development of new therapeutic strategies in sepsis.

Citing Articles

Immature Platelets and Platelet Reactivity in Patients with COVID-19.

Balmakov Y, Mark T, Barnett I, Cipok M, Lev E, Cohen A Clin Appl Thromb Hemost. 2025; 31:10760296251318320.

PMID: 39943824 PMC: 11826839. DOI: 10.1177/10760296251318320.

Multifunctional hyaluronic acid-based biomimetic/pH-responsive hybrid nanostructured lipid carriers for treating bacterial sepsis.

Elhassan E, Omolo C, Gafar M, Ismail E, Ibrahim U, Khan R J Biomed Sci. 2025; 32(1):19.

PMID: 39930418 PMC: 11812216. DOI: 10.1186/s12929-024-01114-6.

Identification of DNA damage repair-related genes in sepsis using bioinformatics and machine learning: An observational study.

Gu J, Wang D, Lou J Medicine (Baltimore). 2025; 104(5):e41354.

PMID: 39889168 PMC: 11789855. DOI: 10.1097/MD.0000000000041354.

Lipopolysaccharide-Neutralizing Peptide Modulates P2X7 Receptor-Mediated Interleukin-1β Release.

Engelhardt J, Klawonn A, Dobbelstein A, Abdelrahman A, Oldenburg J, Brandenburg K ACS Pharmacol Transl Sci. 2025; 8(1):136-145.

PMID: 39816791 PMC: 11729421. DOI: 10.1021/acsptsci.4c00496.

IL-6 and PD-1 antibody blockade combination therapy regulate inflammation and T lymphocyte apoptosis in murine model of sepsis.

Lee S, Kim N, Chung C, Park D, Kang D, Kim D BMC Immunol. 2025; 26(1):3.

PMID: 39806304 PMC: 11731149. DOI: 10.1186/s12865-024-00679-z.

References

Broz P, Newton K, Lamkanfi M, Mariathasan S, Dixit V, Monack D . Redundant roles for inflammasome receptors NLRP3 and NLRC4 in host defense against Salmonella. J Exp Med. 2010; 207(8):1745-55. PMC: 2916133. DOI: 10.1084/jem.20100257. View

Vincent J, Opal S, Marshall J, Tracey K . Sepsis definitions: time for change. Lancet. 2013; 381(9868):774-5. PMC: 4535310. DOI: 10.1016/S0140-6736(12)61815-7. View

Kim Y, Brinkmann M, Paquet M, Ploegh H . UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes. Nature. 2008; 452(7184):234-8. DOI: 10.1038/nature06726. View

Young R, Malcolm K, Kret J, Caceres S, Poch K, Nichols D . Neutrophil extracellular trap (NET)-mediated killing of Pseudomonas aeruginosa: evidence of acquired resistance within the CF airway, independent of CFTR. PLoS One. 2011; 6(9):e23637. PMC: 3164657. DOI: 10.1371/journal.pone.0023637. View

Creasey A, Chang A, Feigen L, Wun T, Taylor Jr F, Hinshaw L . Tissue factor pathway inhibitor reduces mortality from Escherichia coli septic shock. J Clin Invest. 1993; 91(6):2850-60. PMC: 443354. DOI: 10.1172/JCI116529. View

Aras O, Shet A, Bach R, Hysjulien J, Slungaard A, Hebbel R . Induction of microparticle- and cell-associated intravascular tissue factor in human endotoxemia. Blood. 2004; 103(12):4545-53. DOI: 10.1182/blood-2003-03-0713. View

de Jonge E, Dekkers P, Creasey A, Hack C, Paulson S, Karim A . Tissue factor pathway inhibitor dose-dependently inhibits coagulation activation without influencing the fibrinolytic and cytokine response during human endotoxemia. Blood. 2000; 95(4):1124-9. View

Wiersinga W, Calandra T, Kager L, van der Windt G, Roger T, Le Roy D . Expression and function of macrophage migration inhibitory factor (MIF) in melioidosis. PLoS Negl Trop Dis. 2010; 4(2):e605. PMC: 2821910. DOI: 10.1371/journal.pntd.0000605. View

Oldenburg M, Kruger A, Ferstl R, Kaufmann A, Nees G, Sigmund A . TLR13 recognizes bacterial 23S rRNA devoid of erythromycin resistance-forming modification. Science. 2012; 337(6098):1111-5. DOI: 10.1126/science.1220363. View

10.

Bozza F, Gomes R, Japiassu A, Soares M, Castro-Faria-Neto H, Bozza P . Macrophage migration inhibitory factor levels correlate with fatal outcome in sepsis. Shock. 2004; 22(4):309-13. DOI: 10.1097/01.shk.0000140305.01641.c8. View

11.

Emonts M, Sweep F, Grebenchtchikov N, Geurts-Moespot A, Knaup M, Chanson A . Association between high levels of blood macrophage migration inhibitory factor, inappropriate adrenal response, and early death in patients with severe sepsis. Clin Infect Dis. 2007; 44(10):1321-8. DOI: 10.1086/514344. View

12.

Doyle S, Husebye H, Connolly D, Espevik T, ONeill L, Mcgettrick A . The GOLD domain-containing protein TMED7 inhibits TLR4 signalling from the endosome upon LPS stimulation. Nat Commun. 2012; 3:707. DOI: 10.1038/ncomms1706. View

13.

Peelen L, de Keizer N, Peek N, Scheffer G, van der Voort P, de Jonge E . The influence of volume and intensive care unit organization on hospital mortality in patients admitted with severe sepsis: a retrospective multicentre cohort study. Crit Care. 2007; 11(2):R40. PMC: 2206460. DOI: 10.1186/cc5727. View

14.

Urban C, Ermert D, Schmid M, Abu-Abed U, Goosmann C, Nacken W . Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans. PLoS Pathog. 2009; 5(10):e1000639. PMC: 2763347. DOI: 10.1371/journal.ppat.1000639. View

15.

Yende S, Angus D, Kong L, Kellum J, Weissfeld L, Ferrell R . The influence of macrophage migration inhibitory factor gene polymorphisms on outcome from community-acquired pneumonia. FASEB J. 2009; 23(8):2403-11. PMC: 2717777. DOI: 10.1096/fj.09-129445. View

16.

Fang R, Tsuchiya K, Kawamura I, Shen Y, Hara H, Sakai S . Critical roles of ASC inflammasomes in caspase-1 activation and host innate resistance to Streptococcus pneumoniae infection. J Immunol. 2011; 187(9):4890-9. PMC: 3197964. DOI: 10.4049/jimmunol.1100381. View

17.

Angus D, Lidicker J, Clermont G, Carcillo J, Pinsky M . Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001; 29(7):1303-10. DOI: 10.1097/00003246-200107000-00002. View

18.

de Jong H, van der Poll T, Wiersinga W . The systemic pro-inflammatory response in sepsis. J Innate Immun. 2010; 2(5):422-30. DOI: 10.1159/000316286. View

19.

Levy M, Dellinger R, Townsend S, Linde-Zwirble W, Marshall J, Bion J . The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med. 2010; 36(2):222-31. PMC: 2826633. DOI: 10.1007/s00134-009-1738-3. View

20.

Schroder K, Tschopp J . The inflammasomes. Cell. 2010; 140(6):821-32. DOI: 10.1016/j.cell.2010.01.040. View