Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Critical Care
Published in: Critical Care 1/2016

Open Access 01-12-2016 | Review

The role of neutrophils in immune dysfunction during severe inflammation

Authors: Pieter H. C. Leliefeld, Catharina M. Wessels, Luke P. H. Leenen, Leo Koenderman, Janesh Pillay

Published in: Critical Care | Issue 1/2016

Login to get access

Abstract

Critically ill post-surgical, post-trauma and/or septic patients are characterised by severe inflammation. This immune response consists of both a pro- and an anti-inflammatory component. The pro-inflammatory component contributes to (multiple) organ failure whereas occurrence of immune paralysis predisposes to infections. Strikingly, infectious complications arise in these patients despite the presence of a clear neutrophilia. We propose that dysfunction of neutrophils potentially increases the susceptibility to infections or can result in the inability to clear existing infections. Under homeostatic conditions these effector cells of the innate immune system circulate in a quiescent state and serve as the first line of defence against invading pathogens. In severe inflammation, however, neutrophils are rapidly activated, which affects their functional capacities, such as chemotaxis, phagocytosis, intra-cellular killing, NETosis, and their capacity to modulate adaptive immunity. This review provides an overview of the current understanding of neutrophil dysfunction in severe inflammation. We will discuss the possible mechanisms of downregulation of anti-microbial function, suppression of adaptive immunity by neutrophils and the contribution of neutrophil subsets to immune paralysis.
Literature
1.
Lord JM, Midwinter MJ, Chen Y-F, Belli A, Brohi K, Kovacs EJ, et al. The systemic immune response to trauma: an overview of pathophysiology and treatment. Lancet. 2014;384:1455–65.PubMedPubMedCentralCrossRef
2.
Singer PM, De Santis V, Vitale D, Jeffcoate W. Multiorgan failure is an adaptive, endocrine-mediated, metabolic response to overwhelming systemic inaflammation. Lancet. 2004;364:545–8.PubMedCrossRef
3.
4.
Martin SJ, Yost RJ. Infectious diseases in the critically ill patients. J Pharm Pract. 2011;24:35–43.PubMedCrossRef
5.
Vincent J-L, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009;302:2323–9.PubMedCrossRef
6.
Viale P. Candida colonization and candiduria in critically ill patients in the intensive care unit. Drugs. 2009;69 Suppl 1:51–7.PubMedCrossRef
7.
8.
Cobb JP, Buchman TG, Karl IE, Hotchkiss RS. Molecular biology of multiple organ dysfunction syndrome: injury, adaptation, and apoptosis. Surg Infect (Larchmt). 2000;1:207–13.CrossRef
9.
Dinauer MC. Inherited neutrophil disorders: molecular basis and new therapies. Hematology. 2000;2000:303–18.CrossRef
10.
Anderson DC, Springer TA. Leukocyte adhesion deficiency: an inherited defect in the Mac-1, LFA-1, and p150,95 glycoproteins. Annu Rev Med. 1987;38:175–94.PubMedCrossRef
11.
Kjeldsen L, Calafat J, Borregaard N. Giant granules of neutrophils in Chediak-Higashi syndrome are derived from azurophil granules but not from specific and gelatinase granules. J Leukoc Biol. 1998;64:72–7.PubMed
12.
Holland SM. Chronic granulomatous disease. Hematol Oncol Clin North Am. 2014;27:89–99.CrossRef
13.
Belaaouaj A, McCarthy R, Baumann M, Gao Z, Ley TJ, Abraham SN, et al. Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis. Nat Med. 1998;4:615–8.PubMedCrossRef
14.
Gaut JP, Yeh GC, Tran HD, Byun J, Henderson JP, Richter GM, et al. Neutrophils employ the myeloperoxidase system to generate antimicrobial brominating and chlorinating oxidants during sepsis. Proc Natl Acad Sci U S A. 2001;98:11961–6.PubMedPubMedCentralCrossRef
15.
Chiswick EL, Mella JR, Bernardo J, Remick DG. Acute-phase deaths from murine polymicrobial sepsis are characterized by innate immune suppression rather than exhaustion. J Immunol. 2015;195:3793–802.PubMedCrossRef
16.
Zigmond SH. Mechanisms of sensing chemical gradients by polymorphonuclear leukocytes. Nature. 1974;249:450–2.PubMedCrossRef
17.
Boner A, Zeligs B, Bellanti J. Chemotactic responses of various differentational stages of neutrophils from human cord and adult blood. Infect Immun. 1982;35:921–8.PubMedPubMedCentral
18.
Wierusz-Wysocka B, Wysocki H, Siekierka H, Wykretowicz A, Szczepanik A, Klimas R. Evidence of polymorphonuclear neutrophils (PMN) activation in patients with insulin-dependent diabetes mellitus. J Leukoc Biol. 1987;42:519–23.PubMed
19.
Larson HE, Parry RP, Tyrrell DA. Impaired polymorphonuclear leucocyte chemotaxis after influenza virus infection. Br J Dis Chest. 1980;74:56–62.PubMedCrossRef
20.
Bale JF, Kern ER, Overall JC, Baringer JR. Impaired migratory and chemotactic activity of neutrophils during murine cytomegalovirus infection. J Infect Dis. 1983;148:518–25.PubMedCrossRef
21.
Martin LS, Spira TJ, Orloff SL, Holman RC. Comparison of methods for assessing chemotaxis of monocytes and polymorphonuclear leukocytes isolated from patients with AIDS or AIDS-related conditions. J Leukoc Biol. 1988;44:361–6.PubMed
22.
de Leoratti FMS, Trevelin SC, Cunha FQ, Rocha BC, Costa PAC, Gravina HD, et al. Neutrophil paralysis in plasmodium vivax malaria. PLoS Negl Trop Dis. 2012;6:e1710.PubMedPubMedCentralCrossRef
23.
Reddy RC, Standiford TJ. Effects of sepsis on neutrophil chemotaxis. Curr Opin Hematol. 2010;17:18–24.PubMedCrossRef
24.
Reddy RC, Narala VR, Keshamouni VG, Milam JE, Newstead MW, Standiford TJ. Sepsis-induced inhibition of neutrophil chemotaxis is mediated by activation of peroxisome proliferator-activated receptor-{gamma}. Blood. 2008;112:4250–8.PubMedPubMedCentralCrossRef
25.
Rios-Santos F, Alves-Filho JC, Souto FO, Spiller F, Freitas A, Lotufo CMC, et al. Down-regulation of CXCR2 on neutrophils in severe sepsis is mediated by inducible nitric oxide synthase-derived nitric oxide. Am J Respir Crit Care Med. 2007;175:490–7.PubMedCrossRef
26.
Alves-Filho JC, Sônego F, Souto FO, Freitas A, Verri W, Auxiliadora-Martins M, et al. Interleukin-33 attenuates sepsis by enhancing neutrophil influx to the site of infection. Nat Med. 2010;16:708–12.PubMedCrossRef
27.
Dong YL, Abdullah K, Yan TZ, Rutan T, Broemeling L, Robson M, et al. Effect of thermal injury and sepsis on neutrophil function. J Trauma. 1993;34:417–21.PubMedCrossRef
28.
Butler KL, Ambravaneswaran V, Agrawal N, Bilodeau M, Toner M, Tompkins RG, et al. Burn injury reduces neutrophil directional migration speed in microfluidic devices. PLoS One. 2010;5:e11921.PubMedPubMedCentralCrossRef
29.
Nauseef WM. How human neutrophils kill and degrade microbes: an integrated view. Immunol Rev. 2007;219:88–102.PubMedCrossRef
30.
31.
Bedard K, Krause K-H. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 2007;87:245–313.PubMedCrossRef
32.
Liao Y, Liu P, Guo F, Zhang Z-Y, Zhang Z. Oxidative burst of circulating neutrophils following traumatic brain injury in human. PLoS One. 2013;8:e68963.PubMedPubMedCentralCrossRef
33.
Taylor NJ, Nishtala A, Manakkat Vijay GK, Abeles RD, Auzinger G, Bernal W, et al. Circulating neutrophil dysfunction in acute liver failure. Hepatology. 2013;57:1142–52.PubMedCrossRef
34.
Hietbrink F, Koenderman L, Althuizen M, Pillay J, Kamp V, Leenen LPH. Kinetics of the innate immune response after trauma: implications for the development of late onset sepsis. Shock. 2013;40:21–7.PubMedCrossRef
35.
Botha J, Moore FA, Moore EE, Kim FJ, Banerjee A, Peterson VM. Postinjury neutrophil priming and activation: an early vulnerable window. Surgery. 1995;118:358–64. discussion 364–5.PubMedCrossRef
36.
Taylor JV, Gordon LE, Hall H, Heinzelmann M, Polk HC. Differences between bacterial species shown by simultaneous assessment of neutrophil phagocytosis and generation of reactive oxygen intermediates in trauma patients. Arch Surg. 1999;134:1222–7. discussion 1227–8.PubMedCrossRef
37.
Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal. 2014;20:1126–67.PubMedPubMedCentralCrossRef
38.
Fox ED, Heffernan DS, Cioffi WG, Reichner JS. Neutrophils from critically ill septic patients mediate profound loss of endothelial barrier integrity. Crit Care. 2013;17:R226.PubMedPubMedCentralCrossRef
39.
Simms HH, D’Amico R. Increased PMN CD11b/CD18 expression following post-traumatic ARDS. J Surg Res. 1991;50:362–7.PubMedCrossRef
40.
Santos SS, Brunialti MKC, Rigato O, Machado FR, Silva E, Salomao R. Generation of nitric oxide and reactive oxygen species by neutrophils and monocytes from septic patients and association with outcomes. Shock. 2012;38:18–23.PubMedCrossRef
41.
Borregaard N, Cowland JB. Granules of the human neutrophilic polymorphonuclear leukocyte. Blood. 1997;89:3503–21.PubMed
42.
Spicer SS, Hardin JH. Ultrastructure, cytochemistry, and function of neutrophil leukocyte granules. A Rev Lab Invest. 1969;20:488–97.
43.
Levine AP, Duchen MR, de Villiers S, Rich PR, Segal AW. Alkalinity of neutrophil phagocytic vacuoles is modulated by HVCN1 and has consequences for myeloperoxidase activity. PLoS One. 2015;10:e0125906.PubMedPubMedCentralCrossRef
44.
Cech P, Lehrer RI. Phagolysosomal pH of human neutrophils. Blood. 1984;63:88–95.PubMed
45.
Bassøe CF, Laerum OD, Glette J, Hopen G, Haneberg B, Solberg CO. Simultaneous measurement of phagocytosis and phagosomal pH by flow cytometry: role of polymorphonuclear neutrophilic leukocyte granules in phagosome acidification. Cytometry. 1983;4:254–62.PubMedCrossRef
46.
Nanda A, Brumell JH, Nordström T, Kjeldsen L, Sengelov H, Borregaard N, et al. Activation of proton pumping in human neutrophils occurs by exocytosis of vesicles bearing vacuolar-type H + −ATPases. J Biol Chem. 1996;271:15963–70.PubMedCrossRef
47.
Bjerknes R, Vindenes H, Pitkänen J, Ninnemann J, Laerum OD, Abyholm F. Altered polymorphonuclear neutrophilic granulocyte functions in patients with large burns. J Trauma. 1989;29:847–55.PubMedCrossRef
48.
49.
50.
51.
Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, et al. Neutrophil extracellular traps kill bacteria. Science. 2004;303:1532–5.PubMedCrossRef
52.
Remijsen Q, Vanden Berghe T, Wirawan E, Asselbergh B, Parthoens E, De Rycke R, et al. Neutrophil extracellular trap cell death requires both autophagy and superoxide generation. Cell Res. 2011;21:290–304.PubMedCrossRef
53.
Fuchs TA, Abed U, Goosmann C, Hurwitz R, Schulze I, Wahn V, et al. Novel cell death program leads to neutrophil extracellular traps. J Cell Biol. 2007;176:231–41.PubMedPubMedCentralCrossRef
54.
Remijsen Q, Kuijpers TW, Wirawan E, Lippens S, Vandenabeele P, Vanden BT. Dying for a cause: NETosis, mechanisms behind an antimicrobial cell death modality. Cell Death Differ. 2011;18:581–8.PubMedPubMedCentralCrossRef
55.
Yipp BG, Petri B, Salina D, Jenne CN, Scott BNV, Zbytnuik LD, et al. Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo. Nat Med. 2012;18:1386–93.PubMedPubMedCentralCrossRef
56.
Menegazzi R, Decleva E, Dri P. Killing by neutrophil extracellular traps: fact or folklore? Blood. 2012;119:1214–6.PubMedCrossRef
57.
Liu F-C, Chuang Y-H, Tsai Y-F, Yu H-P. Role of neutrophil extracellular traps following injury. Shock. 2014;41:491–8.PubMedCrossRef
58.
Sayah DM, Mallavia B, Liu F, Ortiz-Muñoz G, Caudrillier A, Der Hovanessian A, et al. Neutrophil extracellular traps are pathogenic in primary graft dysfunction after lung transplantation. Am J Respir Crit Care Med. 2015;191:455–63.PubMedPubMedCentralCrossRef
59.
Bosmann M, Ward PA. Protein-based therapies for acute lung injury: targeting neutrophil extracellular traps. Expert Opin Ther Targets. 2014;18:703–14.PubMedPubMedCentralCrossRef
60.
61.
62.
Adams MN, Ramachandran R, Yau MK, Suen JY, Fairlie DP, Hollenberg MD, et al. Structure, function and pathophysiology of protease activated receptors. Pharmacol Ther. 2011;130:248–82.PubMedCrossRef
63.
Steinhoff M, Buddenkotte J, Shpacovitch V, Rattenholl A, Moormann C, Vergnolle N, et al. Proteinase-activated receptors: transducers of proteinase-mediated signaling in inflammation and immune response. Endocr Rev. 2005;26:1–43.PubMedCrossRef
64.
Hartl D, Latzin P, Hordijk P, Marcos V, Rudolph C, Woischnik M, et al. Cleavage of CXCR1 on neutrophils disables bacterial killing in cystic fibrosis lung disease. Nat Med. 2007;13:1423–30.PubMedCrossRef
65.
Quaid G, Cave C, Robinson C, Williams MA, Solomkin J. Preferential loss of CXCR-2 receptor expression and function in patients who have undergone trauma. Arch Surg. 1999;134:1367–71. discussion 1371–2.PubMedCrossRef
66.
Cummings CJ, Martin TR, Frevert CW, Quan JM, Wong VA, Mongovin SM, et al. Expression and function of the chemokine receptors CXCR1 and CXCR2 in sepsis. J Immunol. 1999;162:2341–6.PubMed
67.
Tarlowe MH, Duffy A, Kannan KB, Itagaki K, Lavery RF, Livingston DH, et al. Prospective study of neutrophil chemokine responses in trauma patients at risk for pneumonia. Am J Respir Crit Care Med. 2005;171:753–9.PubMedCrossRef
68.
Sadallah S, Hess C, Miot S, Spertini O, Lutz H, Schifferli JA. Elastase and metalloproteinase activities regulate soluble complement receptor 1 release. Eur J Immunol. 1999;29:3754–61.PubMedCrossRef
69.
van den Berg CW, Tambourgi DV, Clark HW, Hoong SJ, Spiller OB, McGreal EP. Mechanism of neutrophil dysfunction: neutrophil serine proteases cleave and inactivate the C5a receptor. J Immunol. 2014;192:1787–95.PubMedCrossRef
70.
van Kessel KPM, Bestebroer J, van Strijp JAG. Neutrophil-mediated phagocytosis of Staphylococcus aureus. Front Immunol. 2014;5:467.PubMedPubMedCentral
71.
Morris AC, Brittan M, Wilkinson TS, McAuley DF, Antonelli J, McCulloch C, et al. C5a-mediated neutrophil dysfunction is RhoA-dependent and predicts infection in critically ill patients. Blood. 2011;117:5178–88.PubMedCrossRef
72.
Le-Barillec K, Si-Tahar M, Balloy V, Chignard M. Proteolysis of monocyte CD14 by human leukocyte elastase inhibits lipopolysaccharide-mediated cell activation. J Clin Invest. 1999;103:1039–46.PubMedPubMedCentralCrossRef
73.
Bank U, Reinhold D, Schneemilch C, Kunz D, Synowitz HJ, Ansorge S. Selective proteolytic cleavage of IL-2 receptor and IL-6 receptor ligand binding chains by neutrophil-derived serine proteases at foci of inflammation. J Interferon Cytokine Res. 1999;19:1277–87.PubMedCrossRef
74.
75.
Scaffidi P, Misteli T, Bianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature. 2002;418:191–5.PubMedCrossRef
76.
Quintana FJ, Cohen IR. Heat shock proteins as endogenous adjuvants in sterile and septic inflammation. J Immunol. 2005;175:2777–82.PubMedCrossRef
77.
Bours MJL, Swennen ELR, Di Virgilio F, Cronstein BN, Dagnelie PC. Adenosine 5’-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation. Pharmacol Ther. 2006;112:358–404.PubMedCrossRef
78.
Kono H, Chen CJ, Ontiveros F, Rock KL. Uric acid promotes an acute inflammatory response to sterile cell death in mice. J Clin Invest. 2010;120:1939–49.PubMedPubMedCentralCrossRef
79.
Hazeldine J, Hampson P, Opoku FA, Foster M, Lord JM. N-formyl peptides drive mitochondrial damage associated molecular pattern induced neutrophil activation through ERK1/2 and P38 MAP Kinase signalling pathways. Injury. 2015;1–10.
80.
81.
Kumar H, Kawai T, Akira S. Pathogen recognition by the innate immune system. Int Rev Immunol. 2011;30:16–34.PubMedCrossRef
82.
Forsman H, Önnheim K, Andréasson E, Christenson K, Karlsson A, Bylund J, et al. Reactivation of desensitized formyl peptide receptors by platelet activating factor: a novel receptor cross talk mechanism regulating neutrophil superoxide anion production. PLoS One. 2013;8:e60169.PubMedPubMedCentralCrossRef
83.
84.
Pillay J, Ramakers BP, Kamp VM, Loi ALT, Lam SW, Hietbrink F, et al. Functional heterogeneity and differential priming of circulating neutrophils in human experimental endotoxemia. J Leukoc Biol. 2010;88:211–20.PubMedCrossRef
85.
Navarini AA, Lang KS, Verschoor A, Recher M, Zinkernagel AS, Nizet V, et al. Innate immune-induced depletion of bone marrow neutrophils aggravates systemic bacterial infections. Proc Natl Acad Sci U S A. 2009;106:7107–12.PubMedPubMedCentralCrossRef
86.
Taneja R, Sharma AP, Hallett MB, Findlay GP, Morris MR. Immature circulating neutrophils in sepsis have impaired phagocytosis and calcium signaling. Shock. 2008;30:618–22.PubMedCrossRef
87.
Danikas DD, Karakantza M, Theodorou GL, Sakellaropoulos GC, Gogos CA. Prognostic value of phagocytic activity of neutrophils and monocytes in sepsis. Correlation to CD64 and CD14 antigen expression. Clin Exp Immunol. 2008;154:87–97.PubMedPubMedCentralCrossRef
88.
Mare TA, Treacher DF, Shankar-Hari M, Beale R, Lewis SM, Chambers DJ, et al. The diagnostic and prognostic significance of monitoring blood levels of immature neutrophils in patients with systemic inflammation. Crit Care. 2015;19:1–11.CrossRef
89.
Cuenca AG, Delano MJ, Kelly-Scumpia KM, Moreno C, Scumpia PO, Laface DM, et al. A paradoxical role for myeloid-derived suppressor cells in sepsis and trauma. Mol Med. 2011;17:281–92.PubMedCrossRef
90.
91.
Delano MJ, Scumpia PO, Weinstein JS, Coco D, Nagaraj S, Kelly-Scumpia KM, et al. MyD88-dependent expansion of an immature GR-1(+)CD11b(+) population induces T cell suppression and Th2 polarization in sepsis. J Exp Med. 2007;204:1463–74.PubMedPubMedCentralCrossRef
92.
Pelletier M, Maggi L, Micheletti A, Lazzeri E, Tamassia N, Costantini C, et al. Evidence for a cross-talk between human neutrophils and Th17 cells. Blood. 2010;115:335–43.PubMedCrossRef
93.
Chertov O, Yang D, Howard OM, Oppenheim JJ. Leukocyte granule proteins mobilize innate host defenses and adaptive immune responses. Immunol Rev. 2000;177:68–78.PubMedCrossRef
94.
Roghanian A, Drost EM, MacNee W, Howie SEM, Sallenave JM. Inflammatory lung secretions inhibit dendritic cell maturation and function via neutrophil elastase. Am J Respir Crit Care Med. 2006;174:1189–98.PubMedCrossRef
95.
Bank U, Ansorge S. More than destructive: neutrophil-derived serine proteases in cytokine bioactivity control. J Leukoc Biol. 2001;69:197–206.PubMed
96.
Filardy AA, Pires DR, Nunes MP, Takiya CM, Freire-de-Lima CG, Ribeiro-Gomes FL, et al. Proinflammatory clearance of apoptotic neutrophils induces an IL-12(low)IL-10(high) regulatory phenotype in macrophages. J Immunol. 2010;185:2044–50.PubMedCrossRef
97.
Langereis JD, Oudijk EJD, Schweizer RC, Lammers JWJ, Koenderman L, Ulfman LH. Steroids induce a disequilibrium of secreted interleukin-1 receptor antagonist and interleukin-1Beta synthesis by human neutrophils. Eur Respir J. 2011;37:406–15.PubMedCrossRef
98.
Noel G, Wang Q, Schwemberger S, Hanson C, Giacalone N, Haar L, et al. Neutrophils, not monocyte/macrophages, are the major splenic source of postburn IL-10. Shock. 2011;36:149–55.PubMedCrossRef
99.
Davey MS, Tamassia N, Rossato M, Bazzoni F, Calzetti F, Bruderek K, et al. Failure to detect production of IL-10 by activated human neutrophils. Nat Immunol. 2011;12:1017–8. author reply 1018–20.PubMedCrossRef
100.
101.
Pillay J, Tak T, Kamp VM, Koenderman L. Immune suppression by neutrophils and granulocytic myeloid-derived suppressor cells: similarities and differences. Cell Mol Life Sci. 2013;70:3813–27.PubMedPubMedCentralCrossRef
102.
Highfill SL, Rodriguez PC, Zhou Q, Goetz CA, Koehn BH, Veenstra R, et al. Bone marrow myeloid-derived suppressor cells (MDSC) inhibit graft-versus-host (GVHD) disease via an arginase-1 dependent mechanism that is upregulated by IL-13. Blood. 2010;116:612–26.CrossRef
103.
104.
Pillay J, Kamp VM, Van Hoffen E, Visser T, Tak T, Lammers J, et al. A subset of neutrophils in human systemic inflammation inhibits T cell responses through Mac-1. J Clin Invest. 2012;122:327–36.PubMedCrossRef
105.
Darcy CJ, Minigo G, Piera KA, Davis JS, Mcneil YR, Chen Y, et al. Neutrophils with myeloid derived suppressor function deplete arginine and constrain T cell function in septic shock patients. Crit Care. 2014;8(4):R163.CrossRef
106.
de Kleijn S, Langereis JD, Leentjens J, Kox M, Netea MG, Koenderman L, et al. IFN-γ-stimulated neutrophils suppress lymphocyte proliferation through expression of PD-L1. PLoS One. 2013;8:e72249.PubMedPubMedCentralCrossRef
107.
108.
Brahmamdam P, Inoue S, Unsinger J, Chang KC, McDunn JE, Hotchkiss RS. Delayed administration of anti-PD-1 antibody reverses immune dysfunction and improves survival during sepsis. J Leukoc Biol. 2010;88:233–40.PubMedCrossRef
109.
Hampton HR, Bailey J, Tomura M, Brink R, Chtanova T. Microbe-dependent lymphatic migration of neutrophils modulates lymphocyte proliferation in lymph nodes. Nat Commun. 2015;6:7139.PubMedPubMedCentralCrossRef
110.
Kamenyeva O, Boularan C, Kabat J, Cheung GYC, Cicala C, Yeh AJ, et al. Neutrophil recruitment to lymph nodes limits local humoral response to Staphylococcus aureus. PLoS Pathog. 2015;11, e1004827.PubMedPubMedCentralCrossRef
Metadata
Title
The role of neutrophils in immune dysfunction during severe inflammation
Authors
Pieter H. C. Leliefeld
Catharina M. Wessels
Luke P. H. Leenen
Leo Koenderman
Janesh Pillay
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2016
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-016-1250-4

Other articles of this Issue 1/2016

Critical Care 1/2016 Go to the issue

Review

Nomenclature for renal replacement therapy and blood purification techniques in critically ill patients: practical applications

Research

Unexpected versus all-cause mortality as the endpoint for investigating the effects of a Rapid Response System in hospitalized patients

Research

Current real-life use of vasopressors and inotropes in cardiogenic shock - adrenaline use is associated with excess organ injury and mortality

Editorial

Rapid response teams: how are they best used?

Editorial

Fecal microbiota transplantation for multiple organ dysfunction syndrome

Commentary

qSOFA does not replace SIRS in the definition of sepsis