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Published in: Diagnostic Pathology 1/2013

Open Access 01-12-2013 | Research

Triggering receptor expressed on myeloid cells − 1 (Trem-1) on blood neutrophils is associated with cytokine inducibility in human E. coli sepsis

Authors: Tobias van Bremen, Daniel Drömann, Karin Luitjens, Christoph Dodt, Klaus Dalhoff, Torsten Goldmann, Bernhard Schaaf

Published in: Diagnostic Pathology | Issue 1/2013

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Abstract

Background

Bacterial sepsis induced immunsuppression via antigen hyporesponsibility increases the risk of nosokomial infections and mortality. Pattern recognition receptors (PRR) might have a central role in the pathophysiology of hyporesponsibility.

Methods

In this study we evaluated in a human E. coli sepsis cohort, the role of PRR including TLR’s and Trem-1. Expression of Trem-1, TLR2, TLR4, CD14 and HLA-DR on blood monozytes and neutrophils were examined using flow cytometry from 22 patients with E. coli sepsis and 6 healthy controls. LPS and LTA stimulated TNF alpha, IL-10, IL-8 and IL-6 production was studied in a 24 h whole blood assay. Free cytokine serum concentration of TNF alpha, PCT and IP-10 were evaluated.

Results

We found a significant higher expression of Trem-1 and TLR-2 on monocytes and neutrophils in patients compared to healthy volunteers. TLR2 expression (p < 0.05) was higher and HLA-DR lower (p < 0.05) on monocytes of patients with severe sepsis compared to patients with simple sepsis. Trem-1 expression was tendentially higher (p = 0,07) on monocytes and lower on neutrophils of patients with severe sepsis. Trem-1 expression on neutrophils was associated with the IL-10 (LPS: r = 0,61, p < 0.02) and TNF-α inducibility (LPS: r = 0,78, p < 0,002). In addition Trem-1 expression on neutrophils shows a negative correlation to the serum levels of TNF alpha (r = −0,63; p < 0,005), IP-10 (r = −0,5; p < 0,035) and procalcitonin (r = −0,59; p < 0,007).

Conclusions

Patients with E. coli sepsis are characterized by an association of Trem-1 expression on blood neutrophils with cytokine inducibility. The TREM-1 pathway on neutrophils might play a role in producing an adequate inflammatory and bactericidal response in bacterial sepsis.

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Literature
1.
go back to reference Hagel S, Brunkhorst FM: Sepsis. Intensivmed. 2011, 48: 57-73. 10.1007/s00390-010-0249-3.CrossRef Hagel S, Brunkhorst FM: Sepsis. Intensivmed. 2011, 48: 57-73. 10.1007/s00390-010-0249-3.CrossRef
2.
go back to reference Manthey CL, Vogel SN: Interactions of lipopolysaccharide with macrophages. Immunol Ser. 1994, 60: 63-81.PubMed Manthey CL, Vogel SN: Interactions of lipopolysaccharide with macrophages. Immunol Ser. 1994, 60: 63-81.PubMed
3.
go back to reference Sessler CN, Bloomfield GL, Fowler AA: Current concepts of sepsis and acute lung injury. Clin Chest Med. 1996, 12: 213-235.CrossRef Sessler CN, Bloomfield GL, Fowler AA: Current concepts of sepsis and acute lung injury. Clin Chest Med. 1996, 12: 213-235.CrossRef
4.
go back to reference Munford RS, Pugin J: Normal responses to injury prevent systemic inflammation and can be immunosuppressive. Am J Respir Crit Care Med. 2001, 163: 316-321.CrossRefPubMed Munford RS, Pugin J: Normal responses to injury prevent systemic inflammation and can be immunosuppressive. Am J Respir Crit Care Med. 2001, 163: 316-321.CrossRefPubMed
5.
go back to reference West MA, Heagy W: Endotoxin tolerance: a review. CritCare Med. 2002, 30 (1 Suppl.): S64-S73.CrossRef West MA, Heagy W: Endotoxin tolerance: a review. CritCare Med. 2002, 30 (1 Suppl.): S64-S73.CrossRef
6.
go back to reference Härter L, Mica L, Stocker R, Trentz O, Keel M: Increased expression of toll-like receptor-2 and −4 on leukocytes from patients wit sepsis. Shock. 2004, 22: 403-409. 10.1097/01.shk.0000142256.23382.5d.CrossRefPubMed Härter L, Mica L, Stocker R, Trentz O, Keel M: Increased expression of toll-like receptor-2 and −4 on leukocytes from patients wit sepsis. Shock. 2004, 22: 403-409. 10.1097/01.shk.0000142256.23382.5d.CrossRefPubMed
7.
go back to reference Lehner MD, Morath S, Michelsen KS, Schumann RR, Hartung T: Induction of cross-tolerance by lipopolysaccharide and highly purified lipoteichoic acid via different Toll-like receptors independent of paracrine mediators. J Immunol. 2001, 166: 5161-5167.CrossRefPubMed Lehner MD, Morath S, Michelsen KS, Schumann RR, Hartung T: Induction of cross-tolerance by lipopolysaccharide and highly purified lipoteichoic acid via different Toll-like receptors independent of paracrine mediators. J Immunol. 2001, 166: 5161-5167.CrossRefPubMed
8.
go back to reference Nomura F, Akashi S, Sakao Y, Sato S, Kawai T, Matsumoto M, Nakanishi K, Kimoto M, Miyake K, Takeda K, Akira S: Cutting edge: endotoxin tolerance in mouse peritoneal macrophages correlates with down-regulation of surface toll-like receptor 4 expression. J Immunol. 2000, 164: 3476-3479.CrossRefPubMed Nomura F, Akashi S, Sakao Y, Sato S, Kawai T, Matsumoto M, Nakanishi K, Kimoto M, Miyake K, Takeda K, Akira S: Cutting edge: endotoxin tolerance in mouse peritoneal macrophages correlates with down-regulation of surface toll-like receptor 4 expression. J Immunol. 2000, 164: 3476-3479.CrossRefPubMed
9.
go back to reference Oku R, Oda S, Nakada TA, Sadahiro T, Nakamura M, Hirayama Y, Abe R, Tateishi Y, Ito M, Iseki T, Hirasawa H: Differential pattern of cell-surface and soluble TREM-1 between sepsis and SIRS. Cytokine. 2013, 61: 112-117. 10.1016/j.cyto.2012.09.003.CrossRefPubMed Oku R, Oda S, Nakada TA, Sadahiro T, Nakamura M, Hirayama Y, Abe R, Tateishi Y, Ito M, Iseki T, Hirasawa H: Differential pattern of cell-surface and soluble TREM-1 between sepsis and SIRS. Cytokine. 2013, 61: 112-117. 10.1016/j.cyto.2012.09.003.CrossRefPubMed
10.
go back to reference Uehara A, Sato T, Iwashiro A, Yokota S: PR3-ANCA in Wegener’s granulomatosis prime human mononuclear cells for enhanced activation via TLRs and NOD1/2. Diagn Pathol. 2009, 4: 23-10.1186/1746-1596-4-23.PubMedCentralCrossRefPubMed Uehara A, Sato T, Iwashiro A, Yokota S: PR3-ANCA in Wegener’s granulomatosis prime human mononuclear cells for enhanced activation via TLRs and NOD1/2. Diagn Pathol. 2009, 4: 23-10.1186/1746-1596-4-23.PubMedCentralCrossRefPubMed
11.
go back to reference Schaaf B, Luitjens K, Goldmann T, van Bremen T, Sayk F, Dodt C, Dalhoff K, Droemann D: Mortality in human sepsis is associated with downregulation of Toll-like receptor 2 and CD14 expression on blood monocytes. Diagn Pathol. 2009, 4: 12-10.1186/1746-1596-4-12.PubMedCentralCrossRefPubMed Schaaf B, Luitjens K, Goldmann T, van Bremen T, Sayk F, Dodt C, Dalhoff K, Droemann D: Mortality in human sepsis is associated with downregulation of Toll-like receptor 2 and CD14 expression on blood monocytes. Diagn Pathol. 2009, 4: 12-10.1186/1746-1596-4-12.PubMedCentralCrossRefPubMed
12.
go back to reference Lukaszewicz AC, Grienay M, Resche-Rigon M, Pirracchio R, Faivre V, Boval B, Payen D: Monocytic HLA-DR expression in intensive care patients: interest for prognosis and secondary infection prediction. Crit Care Med. 2009, 37: 2746-2752. 10.1097/CCM.0b013e3181ab858a.CrossRefPubMed Lukaszewicz AC, Grienay M, Resche-Rigon M, Pirracchio R, Faivre V, Boval B, Payen D: Monocytic HLA-DR expression in intensive care patients: interest for prognosis and secondary infection prediction. Crit Care Med. 2009, 37: 2746-2752. 10.1097/CCM.0b013e3181ab858a.CrossRefPubMed
13.
go back to reference Barraud D, Gibot S: Triggering receptor expressed on myeloid cell 1. Crit Care Clin. 2011, 27: 265-279. 10.1016/j.ccc.2010.12.006.CrossRefPubMed Barraud D, Gibot S: Triggering receptor expressed on myeloid cell 1. Crit Care Clin. 2011, 27: 265-279. 10.1016/j.ccc.2010.12.006.CrossRefPubMed
14.
go back to reference Bouchon A, Dietrich J, Colonna M: Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes. J Immunol. 2000, 164: 4991-4995.CrossRefPubMed Bouchon A, Dietrich J, Colonna M: Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes. J Immunol. 2000, 164: 4991-4995.CrossRefPubMed
15.
go back to reference Wang F, Liu S, Wu S, Zhu Q, Ou G, Liu C, Wang Y, Liao Y, Sun Z: Blocking TREM-1 signaling prolongs survival of mice with Pseudomonas aeruginosa induced sepsis. Cell Immunol. 2012, 272: 251-258. 10.1016/j.cellimm.2011.10.006.CrossRefPubMed Wang F, Liu S, Wu S, Zhu Q, Ou G, Liu C, Wang Y, Liao Y, Sun Z: Blocking TREM-1 signaling prolongs survival of mice with Pseudomonas aeruginosa induced sepsis. Cell Immunol. 2012, 272: 251-258. 10.1016/j.cellimm.2011.10.006.CrossRefPubMed
16.
go back to reference Gibot S, Massin F, Marcou M, Taylor V, Stidwill R, Wilson P, Singer M, Bellingan G: TREM-1 promotes survival during septic shock in mice. Eur J Immunol. 2007, 37: 456-466. 10.1002/eji.200636387.CrossRefPubMed Gibot S, Massin F, Marcou M, Taylor V, Stidwill R, Wilson P, Singer M, Bellingan G: TREM-1 promotes survival during septic shock in mice. Eur J Immunol. 2007, 37: 456-466. 10.1002/eji.200636387.CrossRefPubMed
17.
go back to reference Bone RC: The sepsis syndrome. Definition and general approach to management. Clin Chest Med. 1996, 17: 175-181. 10.1016/S0272-5231(05)70307-5.CrossRefPubMed Bone RC: The sepsis syndrome. Definition and general approach to management. Clin Chest Med. 1996, 17: 175-181. 10.1016/S0272-5231(05)70307-5.CrossRefPubMed
18.
go back to reference Dalhoff K, Hansen F, Drömann D, Schaaf B, Aries SP, Braun J: Inhibition of neutrophil apoptosis and modulation of the inflammatory response by granulocyte colony-stimulating factor in healthy and ethanol-treated human volunteers. J Infect Dis. 1998, 178: 891-895. 10.1086/515350.CrossRefPubMed Dalhoff K, Hansen F, Drömann D, Schaaf B, Aries SP, Braun J: Inhibition of neutrophil apoptosis and modulation of the inflammatory response by granulocyte colony-stimulating factor in healthy and ethanol-treated human volunteers. J Infect Dis. 1998, 178: 891-895. 10.1086/515350.CrossRefPubMed
19.
go back to reference Kovach MA, Standiford TJ: The function of neutrophils in sepsis. Curr Opin Infect Dis. 2012, 25: 321-327. 10.1097/QCO.0b013e3283528c9b.CrossRefPubMed Kovach MA, Standiford TJ: The function of neutrophils in sepsis. Curr Opin Infect Dis. 2012, 25: 321-327. 10.1097/QCO.0b013e3283528c9b.CrossRefPubMed
20.
go back to reference Tessarz AS, Weiler S, Zanzinger K, Angelisová P, Horejsí V, Cerwenka A: Non-T cell activation linker (NTAL) negatively regulates TREM-1/DAP12-induced inflammatory cytokine production in myeloid cells. J Immunol. 2007, 178: 1991-1999.CrossRefPubMed Tessarz AS, Weiler S, Zanzinger K, Angelisová P, Horejsí V, Cerwenka A: Non-T cell activation linker (NTAL) negatively regulates TREM-1/DAP12-induced inflammatory cytokine production in myeloid cells. J Immunol. 2007, 178: 1991-1999.CrossRefPubMed
21.
go back to reference Bleharski JR, Kiessler V, Buonsanti C, Sieling PA, Stenger S, Colonna M, Modlin RL: A role for triggering receptor expressed on myeloid cells-1 in host defense during the early-induced and adaptive phases of the immune response. J Immunol. 2003, 170: 3812-3818.CrossRefPubMed Bleharski JR, Kiessler V, Buonsanti C, Sieling PA, Stenger S, Colonna M, Modlin RL: A role for triggering receptor expressed on myeloid cells-1 in host defense during the early-induced and adaptive phases of the immune response. J Immunol. 2003, 170: 3812-3818.CrossRefPubMed
22.
go back to reference Su L, Liu C, Li C, Jiang Z, Xiao K, Zhang X, Li M, Yan P, Feng D, Xie L: Dynamic changes in serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and its gene polymorphisms are associated with sepsis prognosis. Inflammation. 2012, 35: 1833-1843. 10.1007/s10753-012-9504-z.CrossRefPubMed Su L, Liu C, Li C, Jiang Z, Xiao K, Zhang X, Li M, Yan P, Feng D, Xie L: Dynamic changes in serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and its gene polymorphisms are associated with sepsis prognosis. Inflammation. 2012, 35: 1833-1843. 10.1007/s10753-012-9504-z.CrossRefPubMed
23.
go back to reference Derive M, Bouazza Y, Sennoun N, Marchionni S, Quigley L, Washington V, Massin F, Max JP, Ford J, Alauzet C, Levy B, McVicar DW, Gibot S: Soluble TREM-like transcript-1 regulates leukocyte activation and controls microbial sepsis. J Immunol. 2012, 188: 5585-5592. 10.4049/jimmunol.1102674.CrossRefPubMed Derive M, Bouazza Y, Sennoun N, Marchionni S, Quigley L, Washington V, Massin F, Max JP, Ford J, Alauzet C, Levy B, McVicar DW, Gibot S: Soluble TREM-like transcript-1 regulates leukocyte activation and controls microbial sepsis. J Immunol. 2012, 188: 5585-5592. 10.4049/jimmunol.1102674.CrossRefPubMed
24.
go back to reference Jeong SJ, Song YG, Kim CO, Kim HW, Ku NS, Han SH, Choi JY, Kim JM: Measurement of plasma sTREM-1 in patients with severe sepsis receiving early goal-directed therapy and evaluation of its usefulness. Shock. 2012, 37: 574-578. 10.1097/SHK.0b013e318250da40.CrossRefPubMed Jeong SJ, Song YG, Kim CO, Kim HW, Ku NS, Han SH, Choi JY, Kim JM: Measurement of plasma sTREM-1 in patients with severe sepsis receiving early goal-directed therapy and evaluation of its usefulness. Shock. 2012, 37: 574-578. 10.1097/SHK.0b013e318250da40.CrossRefPubMed
25.
go back to reference Gómez-Piña V, Soares-Schanoski A, Rodríguez-Rojas A, Del Fresno C, García F, Vallejo-Cremades MT, Fernández-Ruiz I, Arnalich F, Fuentes-Prior P, López-Collazo E: Metalloproteinases shed TREM-1 ectodomain from lipopolysaccharide-stimulated human monocytes. J Immunol. 2007, 179: 4065-4073.CrossRefPubMed Gómez-Piña V, Soares-Schanoski A, Rodríguez-Rojas A, Del Fresno C, García F, Vallejo-Cremades MT, Fernández-Ruiz I, Arnalich F, Fuentes-Prior P, López-Collazo E: Metalloproteinases shed TREM-1 ectodomain from lipopolysaccharide-stimulated human monocytes. J Immunol. 2007, 179: 4065-4073.CrossRefPubMed
26.
go back to reference Fumeaux T, Dufour J, Stern S, Pugin J: Immune monitoring of patients with septic shock by measurement of intraleukocyte cytokines. Intensive Care Med. 2004, 30: 2028-2037. 10.1007/s00134-004-2429-8.CrossRefPubMed Fumeaux T, Dufour J, Stern S, Pugin J: Immune monitoring of patients with septic shock by measurement of intraleukocyte cytokines. Intensive Care Med. 2004, 30: 2028-2037. 10.1007/s00134-004-2429-8.CrossRefPubMed
27.
go back to reference Adib-Conquy M, Cavaillon JM: Host inflammatory and anti-inflammatory response during sepsis. Pathol Biol (Paris). 2012, 60: 306-313. 10.1016/j.patbio.2012.03.011.CrossRef Adib-Conquy M, Cavaillon JM: Host inflammatory and anti-inflammatory response during sepsis. Pathol Biol (Paris). 2012, 60: 306-313. 10.1016/j.patbio.2012.03.011.CrossRef
28.
go back to reference Tsujimoto H, Ono S, Efron PA, Scumpia PO, Moldawer LL, Mochizuki H: Role of toll-like receptors in the development of sepsis. Shock. 2008, 29: 315-321.PubMed Tsujimoto H, Ono S, Efron PA, Scumpia PO, Moldawer LL, Mochizuki H: Role of toll-like receptors in the development of sepsis. Shock. 2008, 29: 315-321.PubMed
29.
go back to reference Trimmel H, Luschin U, Köhrer K, Anzur C, Vevera D, Spittler A: Clinical outcome of critically ill patients cannot be defined by cutoff values of monocyte human leukocyte antigen-DR expression. Shock. 2012, 37: 140-144. 10.1097/SHK.0b013e31823f1866.CrossRefPubMed Trimmel H, Luschin U, Köhrer K, Anzur C, Vevera D, Spittler A: Clinical outcome of critically ill patients cannot be defined by cutoff values of monocyte human leukocyte antigen-DR expression. Shock. 2012, 37: 140-144. 10.1097/SHK.0b013e31823f1866.CrossRefPubMed
30.
go back to reference Palazzo SJ, Simpson T, Schnapp LM: Triggering receptor expressed on myeloid cells type 1 as a potential therapeutic target in sepsis. Dimens Crit Care Nurs. 2012, 31: 1-6. 10.1097/DCC.0b013e31823a5298.CrossRefPubMed Palazzo SJ, Simpson T, Schnapp LM: Triggering receptor expressed on myeloid cells type 1 as a potential therapeutic target in sepsis. Dimens Crit Care Nurs. 2012, 31: 1-6. 10.1097/DCC.0b013e31823a5298.CrossRefPubMed
Metadata
Title
Triggering receptor expressed on myeloid cells − 1 (Trem-1) on blood neutrophils is associated with cytokine inducibility in human E. coli sepsis
Authors
Tobias van Bremen
Daniel Drömann
Karin Luitjens
Christoph Dodt
Klaus Dalhoff
Torsten Goldmann
Bernhard Schaaf
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2013
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/1746-1596-8-24

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