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Bisiaux A, Boussier J, Duffy D, et al. Deconvolution of the Response to Bacillus Calmette-Guérin Reveals NF-κB-Induced Cytokines As Autocrine Mediators of Innate Immunity. Front Immunol. 2017;8:796doi: 10.3389/fimmu.2017.00796.
Bisiaux, A., Boussier, J., Duffy, D., Quintana-Murci, L., Fontes, M., Albert, M. L. (2017). Deconvolution of the Response to Bacillus Calmette-Guérin Reveals NF-κB-Induced Cytokines As Autocrine Mediators of Innate Immunity. Frontiers in immunology, 8796. https://doi.org/10.3389/fimmu.2017.00796
Bisiaux, Aurélie, et al. "Deconvolution of the Response to Bacillus Calmette-Guérin Reveals NF-κB-Induced Cytokines As Autocrine Mediators of Innate Immunity." Frontiers in immunology vol. 8 (2017): 796. doi: https://doi.org/10.3389/fimmu.2017.00796
Bisiaux A, Boussier J, Duffy D, Quintana-Murci L, Fontes M, Albert ML. Deconvolution of the Response to Bacillus Calmette-Guérin Reveals NF-κB-Induced Cytokines As Autocrine Mediators of Innate Immunity. Front Immunol. 2017 Jul 13;8:796. doi: 10.3389/fimmu.2017.00796. eCollection 2017. PMID: 28751891; PMCID: PMC5507989.
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Front Immunol. 2017 Jul 13;8:796. doi: 10.3389/fimmu.2017.00796. eCollection 2017.

Deconvolution of the Response to Bacillus Calmette-Guérin Reveals NF-κB-Induced Cytokines As Autocrine Mediators of Innate Immunity.

Frontiers in immunology

Aurélie Bisiaux, Jeremy Boussier, Darragh Duffy, Lluis Quintana-Murci, Magnus Fontes, Matthew L Albert,

Affiliations

  1. INSERM U1223, Paris, France.
  2. Laboratory of Dendritic Cell Immunobiology, Department of Immunology, Institut Pasteur, Paris, France.
  3. International Group for Data Analysis, Institut Pasteur, Paris, France.
  4. Laboratory of Human Evolutionary Genetics, Department of Genomes and Genetics, Institut Pasteur, Paris, France.
  5. CNRS URA3012, Paris, France.
  6. Department of Immunology, Genentech Inc., South San Francisco, CA, United States.

PMID: 28751891 PMCID: PMC5507989 DOI: 10.3389/fimmu.2017.00796

Abstract

Bacillus Calmette-Guérin (BCG) is used as a vaccine and diagnostic test for tuberculosis, as well as immunotherapy in the treatment of bladder cancer. While clinically useful, the response to mycobacterial stimulation is complex and the induced protein signature remains poorly defined. We characterized the cell types directly engaged by BCG, as well as the induced cytokine loops that transmit signal(s) to bystander cells. Standardized whole-blood stimulations and mechanistic studies on single and purified cell populations identified distinct patterns of activation in monocytes as compared to neutrophils and invariant lymphocyte populations. Deconvoluting the role of Toll-like receptor 2/4 and Dectin-1/2 in the inflammatory response to BCG, we revealed Dectin-1/2 as dominant in neutrophils as compared to monocytes, which equally engaged both pathways. Furthermore, we quantified the role of NF-κB and NADPH/reactive oxygen species (ROS)-dependent cytokines, which triggered a JAK1/2-dependent amplification loop and accounted for 40-50% of the induced response to BCG. In sum, this study provides new insight into the molecular and cellular pathways involved in the response to BCG, establishing the basis for a new generation of immunodiagnostic tools.

Keywords: Dectin-1/2; Jak-1/2 inhibitors; immune monitoring; mycobacteria; toll-like receptors

References

  1. Immunol Rev. 2007 Oct;219:75-87 - PubMed
  2. Microbes Infect. 2014 Dec;16(12):991-7 - PubMed
  3. Eur J Immunol. 2005 May;35(5):1539-47 - PubMed
  4. N Engl J Med. 2010 Sep 16;363(12):1117-27 - PubMed
  5. Mucosal Immunol. 2011 May;4(3):252-60 - PubMed
  6. Trends Immunol. 2017 Jan;38(1):66-76 - PubMed
  7. Curr Drug Targets. 2008 Feb;9(2):123-9 - PubMed
  8. Clin Infect Dis. 2000 Sep;31 Suppl 3:S86-90 - PubMed
  9. Metabolism. 2012 Nov;61(11):1538-46 - PubMed
  10. Clin Exp Immunol. 1999 Jan;115(1):131-5 - PubMed
  11. Immunity. 2014 Mar 20;40(3):436-50 - PubMed
  12. Sci Transl Med. 2012 Jun 6;4(137):137ra72 - PubMed
  13. Bioinformatics. 2009 Aug 15;25(16):2020-7 - PubMed
  14. Ann Rheum Dis. 2013 Apr;72 Suppl 2:ii111-5 - PubMed
  15. J Urol. 2003 May;169(5):1702-5 - PubMed
  16. Nature. 2011 Apr 28;472(7344):471-5 - PubMed
  17. Cell. 2010 Mar 19;140(6):805-20 - PubMed
  18. PLoS Med. 2011 Mar;8(3):e1001012 - PubMed
  19. Biochem Pharmacol. 2006 Nov 30;72(11):1493-505 - PubMed
  20. Vaccine. 2010 Feb 10;28(6):1635-41 - PubMed
  21. Nat Rev Urol. 2013 Sep;10(9):537-45 - PubMed
  22. Nature. 2001 Apr 26;410(6832):1099-103 - PubMed
  23. Cell Host Microbe. 2015 Jun 10;17 (6):811-819 - PubMed
  24. Blood. 2006 Nov 1;108(9):3168-75 - PubMed
  25. Cell Rep. 2016 Sep 6;16(10):2777-91 - PubMed
  26. Tuber Lung Dis. 2000;80(4-5):197-207 - PubMed
  27. Nat Commun. 2015 Apr 21;6:6847 - PubMed
  28. J Biol Chem. 2002 Feb 22;277(8):6059-66 - PubMed
  29. J Infect. 2003 Aug;47(2):139-47 - PubMed
  30. Clin Immunol. 2015 Apr;157(2):277-93 - PubMed
  31. J Cell Sci. 2004 Mar 15;117(Pt 8):1281-3 - PubMed
  32. Immunity. 2014 Sep 18;41(3):402-13 - PubMed
  33. Cell Res. 2011 Jan;21(1):103-15 - PubMed
  34. Infect Immun. 2000 Dec;68(12):6883-90 - PubMed
  35. Biomed Pharmacother. 2007 Jul;61(6):299-305 - PubMed
  36. Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2434-9 - PubMed
  37. Clin Dev Immunol. 2011;2011:405310 - PubMed
  38. J Immunol. 2011 May 15;186(10):5916-26 - PubMed
  39. J Urol. 1976 Aug;116(2):180-3 - PubMed
  40. Ann Intern Med. 2008 Aug 5;149(3):177-84 - PubMed
  41. J Immunol. 2007 Jan 15;178(2):1164-71 - PubMed
  42. Nat Immunol. 2005 Aug;6(8):769-76 - PubMed

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