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Dysregulated T helper type 1 (Th1) and Th17 responses in elderly hospitalised patients with infection and sepsis


Autoři: John D. Coakley aff001;  Eamon P. Breen aff002;  Ana Moreno-Olivera aff003;  Alhanouf I. Al-Harbi aff003;  A. M. Melo aff003 ;  Brian O’Connell aff004;  Ross McManus aff005;  Derek G. Doherty aff003;  Thomas Ryan aff001
Působiště autorů: Department of Intensive Care Medicine, St James’s Hospital, Dublin, Ireland aff001;  Trinity Translational Medicine Institute, St James’s Hospital, Dublin, Ireland aff002;  Department of Immunology, Trinity Translational Medicine Institute, Dublin, Ireland aff003;  Department of Clinical Microbiology, St James’s Hospital, Dublin, Ireland aff004;  Department of Clinical Medicine and Genetics, Trinity Translational Medicine Institute, Dublin, Ireland aff005
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0224276

Souhrn

Objective

The role of Th1 and Th17 lymphocyte responses in human infection and sepsis of elderly patients has yet to be clarified.

Design

A prospective observational study of patients with sepsis, infection only and healthy controls.

Setting

The acute medical wards and intensive care units in a 1000 bed university hospital.

Patients

32 patients with sepsis, 20 patients with infection, and 20 healthy controls. Patients and controls were older than 65 years of age. Patients with recognised underlying immune compromise were excluded.

Methods

Phenotype, differentiation status and cytokine production by T lymphocytes were determined by flow cytometry.

Measurements

The differentiation states of circulating CD3+, CD4+, and CD8+ T cells were characterised as naive (CD45RA+, CD197+), central memory (CD45RA-, CD197+), effector memory (CD45RA-, CD197-), or terminally differentated (CD45RA+, CD197-). Expression of IL-12 and IL-23 receptors, and the transcription factors T-bet and RORγt, was analysed in circulating T lymphocytes. Expression of interferon- γ and IL-17A were analysed following stimulation in vitro.

Results

CD4+ T cells from patients with infection predominantly expressed effector-memory or terminally differentiated phenotypes but CD4+ T cells from patients with severe sepsis predominantly expressed naive phenotypes (p<0.0001). CD4+ T cells expressing IL-23 receptor were lower in patients with sepsis compared to patients with infection alone (p = 0.007). RORγt expression by CD4+ T cells was less frequent in patients with sepsis (p<0.001), whereas T-bet expressing CD8+ T cells that do not express RORγt was lower in the sepsis patients.

HLA-DR expression by monocytes was lower in patients with sepsis. In septic patients fewer monocytes expressed IL-23.

Conclusion

Persistent failure of T cell activation was observed in patients with sepsis. Sepsis was associated with attenuated CD8+Th1 and CD4+Th17 based lymphocyte response.

Klíčová slova:

Cell differentiation – Transcription factors – Respiratory infections – T cells – Cytotoxic T cells – Lymphocytes – Monocytes – Sepsis


Zdroje

1. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR: Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Critical care medicine 2001, 29(7):1303–1310. doi: 10.1097/00003246-200107000-00002 11445675

2. Fleischmann C, Thomas-Rueddel DO, Hartmann M, Hartog CS, Welte T, Heublein S et al: Hospital Incidence and Mortality Rates of Sepsis. Dtsch Arztebl Int 2016, 113(10):159–166. doi: 10.3238/arztebl.2016.0159 27010950

3. Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W et al: Genomic responses in mouse models poorly mimic human inflammatory diseases. Proceedings of the National Academy of Sciences of the United States of America 2013, 110(9):3507–3512. doi: 10.1073/pnas.1222878110 23401516

4. Hotchkiss RS, Monneret G, Payen D: Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach. The Lancet infectious diseases 2013, 13(3):260–268. doi: 10.1016/S1473-3099(13)70001-X 23427891

5. Venet F, Filipe-Santos O, Lepape A, Malcus C, Poitevin-Later F, Grives A et al: Decreased T-cell repertoire diversity in sepsis: a preliminary study. Critical care medicine 2013, 41(1):111–119. doi: 10.1097/CCM.0b013e3182657948 23222261

6. Lukaszewicz AC, Grienay M, Resche-Rigon M, Pirracchio R, Faivre V, Boval B et al: Monocytic HLA-DR expression in intensive care patients: interest for prognosis and secondary infection prediction. Critical care medicine 2009, 37(10):2746–2752. doi: 10.1097/CCM.0b013e3181ab858a 19707128

7. Hotchkiss RS, Osmon SB, Chang KC, Wagner TH, Coopersmith CM, Karl IE: Accelerated lymphocyte death in sepsis occurs by both the death receptor and mitochondrial pathways. Journal of immunology 2005, 174(8):5110–5118.

8. Monneret G, Lepape A, Voirin N, Bohe J, Venet F, Debard AL et al: Persisting low monocyte human leukocyte antigen-DR expression predicts mortality in septic shock. Intensive Care Med 2006, 32(8):1175–1183. doi: 10.1007/s00134-006-0204-8 16741700

9. Grimaldi D, Louis S, Pene F, Sirgo G, Rousseau C, Claessens YE et al: Profound and persistent decrease of circulating dendritic cells is associated with ICU-acquired infection in patients with septic shock. Intensive Care Med 2011, 37(9):1438–1446. doi: 10.1007/s00134-011-2306-1 21805160

10. Forel JM, Chiche L, Thomas G, Mancini J, Farnarier C, Cognet C et al: Phenotype and functions of natural killer cells in critically-ill septic patients. PloS one 2012, 7(12):e50446. doi: 10.1371/journal.pone.0050446 23236375

11. Hotchkiss RS, Monneret G, Payen D: Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nature reviews Immunology 2013, 13(12):862–874. doi: 10.1038/nri3552 24232462

12. Inoue S, Suzuki-Utsunomiya K, Okada Y, Taira T, Iida Y, Miura N et al: Reduction of immunocompetent T cells followed by prolonged lymphopenia in severe sepsis in the elderly. Critical care medicine 2013, 41(3):810–819. doi: 10.1097/CCM.0b013e318274645f 23328259

13. Venet F, Pachot A, Debard AL, Bohe J, Bienvenu J, Lepape A et al: Increased percentage of CD4+CD25+ regulatory T cells during septic shock is due to the decrease of CD4+CD25- lymphocytes. Critical care medicine 2004, 32(11):2329–2331. doi: 10.1097/01.ccm.0000145999.42971.4b 15640650

14. Faivre V, Lukaszewicz AC, Alves A, Charron D, Payen D, Haziot A: Human monocytes differentiate into dendritic cells subsets that induce anergic and regulatory T cells in sepsis. PloS one 2012, 7(10):e47209. doi: 10.1371/journal.pone.0047209 23071758

15. Zhu J, Yamane H, Paul WE: Differentiation of effector CD4 T cell populations. Annual review of immunology 2010, 28:445–489. doi: 10.1146/annurev-immunol-030409-101212 20192806

16. Damsker JM, Hansen AM, Caspi RR: Th1 and Th17 cells: adversaries and collaborators. Annals of the New York Academy of Sciences 2010, 1183:211–221. doi: 10.1111/j.1749-6632.2009.05133.x 20146717

17. Naylor K, Li G, Vallejo AN, Lee WW, Koetz K, Bryl E et al: The influence of age on T cell generation and TCR diversity. Journal of immunology 2005, 174(11):7446–7452.

18. National Consent Policy. In. Edited by National Consent Advisory Group HSE, Ireland. Dublin, Ireland.; 2017.

19. Zhang M, Gong J, Presky DH, Xue W, Barnes PF: Expression of the IL-12 receptor beta 1 and beta 2 subunits in human tuberculosis. Journal of immunology 1999, 162(4):2441–2447.

20. Chognard G, Bellemare L, Pelletier AN, Dominguez-Punaro MC, Beauchamp C, Guyon MJ et al: The dichotomous pattern of IL-12r and IL-23R expression elucidates the role of IL-12 and IL-23 in inflammation. PloS one 2014, 9(2):e89092. doi: 10.1371/journal.pone.0089092 24586521

21. Venet F, Foray AP, Villars-Mechin A, Malcus C, Poitevin-Later F, Lepape A et al: IL-7 restores lymphocyte functions in septic patients. Journal of immunology 2012, 189(10):5073–5081.

22. Cauvi DM, Williams MR, Bermudez JA, Armijo G, De Maio A: Elevated expression of IL-23/IL-17 pathway-related mediators correlates with exacerbation of pulmonary inflammation during polymicrobial sepsis. Shock 2014, 42(3):246–255. doi: 10.1097/SHK.0000000000000207 24978886

23. Ronit A, Plovsing RR, Gaardbo JC, Berg RM, Hartling HJ, Ullum H et al: Inflammation-Induced Changes in Circulating T-Cell Subsets and Cytokine Production During Human Endotoxemia. Journal of intensive care medicine 2017, 32(1):77–85. doi: 10.1177/0885066615606673 26392625

24. Mikacenic C, Hansen EE, Radella F, Gharib SA, Stapleton RD, Wurfel MM: Interleukin-17A Is Associated With Alveolar Inflammation and Poor Outcomes in Acute Respiratory Distress Syndrome. Critical care medicine 2016, 44(3):496–502. doi: 10.1097/CCM.0000000000001409 26540401

25. Yan Z, Xiaoyu Z, Zhixin S, Di Q, Xinyu D, Jing X et al: Rapamycin attenuates acute lung injury induced by LPS through inhibition of Th17 cell proliferation in mice. Sci Rep 2016, 6:20156. doi: 10.1038/srep20156 26888095

26. Brunialti MK, Santos MC, Rigato O, Machado FR, Silva E, Salomao R: Increased percentages of T helper cells producing IL-17 and monocytes expressing markers of alternative activation in patients with sepsis. PloS one 2012, 7(5):e37393. doi: 10.1371/journal.pone.0037393 22693573

27. Maravitsa P, Adamopoulou M, Pistiki A, Netea MG, Louis K, Giamarellos-Bourboulis EJ: Systemic over-release of interleukin-17 in acute kidney injury after septic shock: Clinical and experimental evidence. Immunology letters 2016, 178:68–76. doi: 10.1016/j.imlet.2016.08.002 27515003

28. Wynn JL, Wilson CS, Hawiger J, Scumpia PO, Marshall AF, Liu JH et al: Targeting IL-17A attenuates neonatal sepsis mortality induced by IL-18. Proceedings of the National Academy of Sciences of the United States of America 2016, 113(19):E2627–2635. doi: 10.1073/pnas.1515793113 27114524

29. Paraschos MD, Patrani M, Pistiki A, Katsenos C, Tsaganos T, Netea MG et al: Defective cytokine production early after multiple traumas: Modulation in severe sepsis. Cytokine 2015, 76(2):222–226. doi: 10.1016/j.cyto.2015.05.021 26082021

30. Breslow JM, Meissler JJ Jr., Hartzell RR, Spence PB, Truant A, Gaughan J et al: Innate immune responses to systemic Acinetobacter baumannii infection in mice: neutrophils, but not interleukin-17, mediate host resistance. Infect Immun 2011, 79(8):3317–3327. doi: 10.1128/IAI.00069-11 21576323

31. Nordfjall K, Larefalk A, Lindgren P, Holmberg D, Roos G: Telomere length and heredity: Indications of paternal inheritance. Proceedings of the National Academy of Sciences of the United States of America 2005, 102(45):16374–16378. doi: 10.1073/pnas.0501724102 16258070

32. Puel A, Cypowyj S, Bustamante J, Wright JF, Liu L, Lim HK et al: Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity. Science 2011, 332(6025):65–68. doi: 10.1126/science.1200439 21350122

33. Milner JD, Brenchley JM, Laurence A, Freeman AF, Hill BJ, Elias KM et al: Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature 2008, 452(7188):773–776. doi: 10.1038/nature06764 18337720

34. Liu B, Tan W, Barsoum A, Gu X, Chen K, Huang W et al: IL-17 is a potent synergistic factor with GM-CSF in mice in stimulating myelopoiesis, dendritic cell expansion, proliferation, and functional enhancement. Experimental hematology 2010, 38(10):877–884 e871. doi: 10.1016/j.exphem.2010.06.004 20600582

35. Shen H, Zhang W, Abraham C, Cho JH: Age and CD161 expression contribute to inter-individual variation in interleukin-23 response in CD8+ memory human T cells. PloS one 2013, 8(3):e57746. doi: 10.1371/journal.pone.0057746 23469228

36. Schmitt V, Rink L, Uciechowski P: The Th17/Treg balance is disturbed during aging. Experimental gerontology 2013, 48(12):1379–1386. doi: 10.1016/j.exger.2013.09.003 24055797

37. Langrish CL, McKenzie BS, Wilson NJ, de Waal Malefyt R, Kastelein RA, Cua DJ: IL-12 and IL-23: master regulators of innate and adaptive immunity. Immunological reviews 2004, 202:96–105. doi: 10.1111/j.0105-2896.2004.00214.x 15546388

38. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD et al: IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. The Journal of experimental medicine 2005, 201(2):233–240. doi: 10.1084/jem.20041257 15657292

39. Cosmi L, De Palma R, Santarlasci V, Maggi L, Capone M, Frosali F et al: Human interleukin 17-producing cells originate from a CD161+CD4+ T cell precursor. The Journal of experimental medicine 2008, 205(8):1903–1916. doi: 10.1084/jem.20080397 18663128


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