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Specific MAIT cell behaviour among innate-like T lymphocytes in critically ill patients with severe infections

David Grimaldi| Lionel Le Bourhis| Bertrand Sauneuf| Agnès Dechartres| Christophe Rousseau| Fatah Ouaaz| Maud Milder| Delphine Louis| Jean-Daniel Chiche| Jean-Paul Mira| Olivier Lantz| Frédéric Pène
Original Article
Volume 40, Issue 2 / February , 2014

Pages 192 - 201

Abstract

Purpose

In between innate and adaptive immunity, the recently identified innate-like mucosal-associated invariant T (MAIT) lymphocytes display specific reactivity to non-streptococcal bacteria. Whether they are involved in bacterial sepsis has not been investigated. We aimed to assess the number and the time course of circulating innate-like T lymphocytes (MAIT, NKT and γδ T cells) in critically ill septic and non-septic patients and to establish correlations with the further development of intensive care unit (ICU)-acquired infections.

Methods

We prospectively enrolled consecutive patients with severe sepsis and septic shock. Controls were critically ill patients with non-septic shock and age-matched healthy subjects. Circulating innate-like lymphocytes were enumerated using a flow cytometry assay at day 1, 4 and 7.

Results

One hundred and fifty six patients (113 severe bacterial infections, 36 non-infected patients and 7 patients with severe viral infections) and 26 healthy subjects were enrolled into the study. Patients with severe bacterial infections displayed an early decrease in MAIT cell count [median 1.3/mm3; interquartile range (0.4–3.2)] as compared to control healthy subjects [31.1/mm3 (12.1–45.2)], but also to non-infected critically ill patients [4.3/mm3 (1.4–13.2)] (P < 0.0001 for all comparisons). In contrast NKT and γδ T cell counts did not differ between patients groups. The multivariate analysis identified non-streptococcal bacterial infection as an independent determinant of decrease in MAIT cell count. Furthermore, the incidence of ICU-acquired infections was higher in patients with persistent MAIT cell depletion.

Conclusions

This large human study provides valuable information about MAIT cells in severe bacterial infections. The persistent depletion of MAIT cells is associated with the further development of ICU-acquired infections.

Keywords

References

  1. Treiner E, Lantz O (2006) CD1d- and MR1-restricted invariant T cells: of mice and men. Curr Opin Immunol 18:519–526
    • View reference on PubMed
    • View reference on publisher's website
  2. Bendelac A, Bonneville M, Kearney JF (2001) Autoreactivity by design: innate B and T lymphocytes. Nat Rev Immunol 1:177–186
    • View reference on PubMed
    • View reference on publisher's website
  3. Bonneville M, Scotet E (2006) Human Vgamma9Vdelta2 T cells: promising new leads for immunotherapy of infections and tumors. Curr Opin Immunol 18:539–546
    • View reference on PubMed
    • View reference on publisher's website
  4. Kawachi I, Maldonado J, Strader C, Gilfillan S (2006) MR1-restricted V alpha 19i mucosal-associated invariant T cells are innate T cells in the gut lamina propria that provide a rapid and diverse cytokine response. J Immunol 176:1618–1627
    • View reference on PubMed
  5. Croxford JL, Miyake S, Huang YY, Shimamura M, Yamamura T (2006) Invariant V(alpha)19i T cells regulate autoimmune inflammation. Nat Immunol 7:987–994
    • View reference on PubMed
    • View reference on publisher's website
  6. Le Bourhis L, Martin E, Peguillet I, Guihot A, Froux N, Core M, Levy E, Dusseaux M, Meyssonnier V, Premel V, Ngo C, Riteau B, Duban L, Robert D, Huang S, Rottman M, Soudais C, Lantz O (2010) Antimicrobial activity of mucosal-associated invariant T cells. Nat Immunol 11:701–708
    • View reference on PubMed
    • View reference on publisher's website
  7. Dusseaux M, Martin E, Serriari N, Peguillet I, Premel V, Louis D, Milder M, Le Bourhis L, Soudais C, Treiner E, Lantz O (2011) Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17-secreting T cells. Blood 117:1250–1259
    • View reference on PubMed
    • View reference on publisher's website
  8. Le Bourhis L, Guerri L, Dusseaux M, Martin E, Soudais C, Lantz O (2011) Mucosal-associated invariant T cells: unconventional development and function. Trends Immunol 32:212–218
    • View reference on PubMed
    • View reference on publisher's website
  9. Grimaldi D (2011) Bacterial sepsis induces a profound depletion in circulating mucosal-associated invariant T (MAIT) lymphocytes (Abstract). Intensive Care Med 37 (Suppl 1):1005
  10. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med 29:530–538
  11. Mermel LA, Farr BM, Sherertz RJ, Raad II, O’Grady N, Harris JS, Craven DE (2001) Guidelines for the management of intravascular catheter-related infections. Clin Infect Dis 32:1249–1272
    • View reference on PubMed
    • View reference on publisher's website
  12. American Thoracic Society, Infectious Diseases Society of America (2005) Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Resp Crit Care Med 171:388–416
  13. Anderson JR, Cain KC, Gelber RD (1983) Analysis of survival by tumor response. J Clin Oncol 1:710–719
    • View reference on PubMed
  14. Fine JP, Gray RJ (1999) A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94:496–509
    • View reference on publisher's website
  15. Kjer-Nielsen L, Patel O, Corbett AJ, Le Nours J, Meehan B, Liu L, Bhati M, Chen Z, Kostenko L, Reantragoon R, Williamson NA, Purcell AW, Dudek NL, McConville MJ, O’Hair RA, Khairallah GN, Godfrey DI, Fairlie DP, Rossjohn J, McCluskey J (2012) MR1 presents microbial vitamin B metabolites to MAIT cells. Nature 491:717–723
    • View reference on PubMed
  16. Cosgrove C, Ussher JE, Rauch A, Gartner K, Kurioka A, Huhn MH, Adelmann K, Kang YH, Fergusson JR, Simmonds P, Goulder P, Hansen TH, Fox J, Gunthard HF, Khanna N, Powrie F, Steel A, Gazzard B, Phillips RE, Frater J, Uhlig H, Klenerman P (2013) Early and nonreversible decrease of CD161++/MAIT cells in HIV infection. Blood 121:951–961
    • View reference on PubMed
    • View reference on publisher's website
  17. Billerbeck E, Kang YH, Walker L, Lockstone H, Grafmueller S, Fleming V, Flint J, Willberg CB, Bengsch B, Seigel B, Ramamurthy N, Zitzmann N, Barnes EJ, Thevanayagam J, Bhagwanani A, Leslie A, Oo YH, Kollnberger S, Bowness P, Drognitz O, Adams DH, Blum HE, Thimme R, Klenerman P (2010) Analysis of CD161 expression on human CD8+ T cells defines a distinct functional subset with tissue-homing properties. Proc Natl Acad Sci U S A 107:3006–3011
    • View reference on PubMed
    • View reference on publisher's website
  18. Asehnoune K, Roquilly A, Abraham E (2012) Innate immune dysfunction in trauma patients: from pathophysiology to treatment. Anesthesiology 117:411–416
    • View reference on PubMed
    • View reference on publisher's website
  19. Grimaldi D, Louis S, Pene F, Sirgo G, Rousseau C, Claessens YE, Vimeux L, Cariou A, Mira JP, Hosmalin A, Chiche JD (2011) Profound and persistent decrease of circulating dendritic cells is associated with ICU-acquired infection in patients with septic shock. Intensive Care Med 37:1438–1446
  20. Landelle C, Lepape A, Voirin N, Tognet E, Venet F, Bohe J, Vanhems P, Monneret G (2010) Low monocyte human leukocyte antigen-DR is independently associated with nosocomial infections after septic shock. Intensive Care Med 36:1859–1866
  21. Lukaszewicz AC, Grienay M, Resche-Rigon M, Pirracchio R, Faivre V, Boval B, Payen D (2009) Monocytic HLA-DR expression in intensive care patients: interest for prognosis and secondary infection prediction. Crit Care Med 37:2746–2752
    • View reference on PubMed
    • View reference on publisher's website
  22. Guignant C, Venet F, Planel S, Demaret J, Gouel-Cheron A, Nougier C, Friggeri A, Allaouchiche B, Lepape A, Monneret G (2013) Increased MerTK expression in circulating innate immune cells of patients with septic shock. Intensive Care Med 39:1556–1564
  23. Guignant C, Lepape A, Huang X, Kherouf H, Denis L, Poitevin F, Malcus C, Cheron A, Allaouchiche B, Gueyffier F, Ayala A, Monneret G, Venet F (2011) Programmed death-1 levels correlate with increased mortality, nosocomial infection and immune dysfunctions in septic shock patients. Crit Care 15:R99
    • View reference on PubMed
    • View reference on publisher's website
  24. Hotchkiss RS, Monneret G, Payen D (2013) Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach. Lancet Infect Dis 13:260–268
    • View reference on PubMed
    • View reference on publisher's website
  25. Georgel P, Radosavljevic M, Macquin C, Bahram S (2011) The non-conventional MHC class I MR1 molecule controls infection by Klebsiella pneumoniae in mice. Mol Immunol 48:769–775
    • View reference on PubMed
    • View reference on publisher's website
  26. Gold MC, Cerri S, Smyk-Pearson S, Cansler ME, Vogt TM, Delepine J, Winata E, Swarbrick GM, Chua WJ, Yu YY, Lantz O, Cook MS, Null MD, Jacoby DB, Harriff MJ, Lewinsohn DA, Hansen TH, Lewinsohn DM (2010) Human mucosal associated invariant T cells detect bacterially infected cells. PLoS Biol 8:e1000407
    • View reference on PubMed
    • View reference on publisher's website
  27. Mattner J, Debord KL, Ismail N, Goff RD, Cantu C 3rd, Zhou D, Saint-Mezard P, Wang V, Gao Y, Yin N, Hoebe K, Schneewind O, Walker D, Beutler B, Teyton L, Savage PB, Bendelac A (2005) Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature 434:525–529
    • View reference on PubMed
    • View reference on publisher's website
  28. Kinjo Y, Wu D, Kim G, Xing GW, Poles MA, Ho DD, Tsuji M, Kawahara K, Wong CH, Kronenberg M (2005) Recognition of bacterial glycosphingolipids by natural killer T cells. Nature 434:520–525
    • View reference on PubMed
    • View reference on publisher's website
  29. Kinjo Y, Tupin E, Wu D, Fujio M, Garcia-Navarro R, Benhnia MR, Zajonc DM, Ben-Menachem G, Ainge GD, Painter GF, Khurana A, Hoebe K, Behar SM, Beutler B, Wilson IA, Tsuji M, Sellati TJ, Wong CH, Kronenberg M (2006) Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria. Nat Immunol 7:978–986
    • View reference on PubMed
    • View reference on publisher's website
  30. Kinjo Y, Illarionov P, Vela JL, Pei B, Girardi E, Li X, Li Y, Imamura M, Kaneko Y, Okawara A, Miyazaki Y, Gomez-Velasco A, Rogers P, Dahesh S, Uchiyama S, Khurana A, Kawahara K, Yesilkaya H, Andrew PW, Wong CH, Kawakami K, Nizet V, Besra GS, Tsuji M, Zajonc DM, Kronenberg M (2011) Invariant natural killer T cells recognize glycolipids from pathogenic Gram-positive bacteria. Nat Immunol 12:966–974
    • View reference on PubMed
    • View reference on publisher's website
  31. Leung B, Harris HW (2011) NKT cells: the culprits of sepsis? J Surg Res 167:87–95
  32. Venet F, Bohe J, Debard AL, Bienvenu J, Lepape A, Monneret G (2005) Both percentage of gammadelta T lymphocytes and CD3 expression are reduced during septic shock. Crit Care Med 33:2836–2840
    • View reference on PubMed
    • View reference on publisher's website
  33. Venet F, Chung CS, Monneret G, Huang X, Horner B, Garber M, Ayala A (2008) Regulatory T cell populations in sepsis and trauma. J Leuk Biol 83:523–535
    • View reference on publisher's website
  34. Deknuydt F, Roquilly A, Cinotti R, Altare F, Asehnoune K (2013) An in vitro model of mycobacterial granuloma to investigate the immune response in brain-injured patients. Crit Care Med 41:245–254
    • View reference on PubMed
    • View reference on publisher's website
  35. Hotchkiss RS, Strasser A, McDunn JE, Swanson PE (2009) Cell death. New Engl J Med 361:1570–1583
    • View reference on PubMed
    • View reference on publisher's website
  36. Venet F, Pachot A, Debard AL, Bohe J, Bienvenu J, Lepape A, Monneret G (2004) Increased percentage of CD4+ CD25+ regulatory T cells during septic shock is due to the decrease of CD4+ CD25− lymphocytes. Crit Care Med 32:2329–2331
    • View reference on PubMed

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