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J Infect Dis. 2014 Dec 01;210(11):1844-54. doi: 10.1093/infdis/jiu290. Epub 2014 May 19.

Dectin-1-dependent LC3 recruitment to phagosomes enhances fungicidal activity in macrophages.

The Journal of infectious diseases

Jenny M Tam, Michael K Mansour, Nida S Khan, Michael Seward, Sravanthi Puranam, Antoine Tanne, Anna Sokolovska, Christine E Becker, Mridu Acharya, Michelle A Baird, Augustine M K Choi, Michael W Davidson, Brahm H Segal, Adam Lacy-Hulbert, Lynda M Stuart, Ramnik J Xavier, Jatin M Vyas

Affiliations

  1. Department of Medicine, Division of Infectious Diseases Department of Medicine, Harvard Medical School, Boston.
  2. Department of Medicine, Division of Infectious Diseases.
  3. Icahn School of Medicine at Mt. Sinai, Tisch Cancer Institute.
  4. Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital.
  5. Gastrointestinal Unit Center for the Study of Inflammatory Bowel Disease Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge.
  6. Benaroya Research Institute, Seattle, Washington.
  7. National High Magnetic Field Laboratory, Florida State University, Tallahassee.
  8. Weill Cornell Medical College.
  9. Roswell Park Cancer Institute, University of Buffalo School of Medicine, New York.

PMID: 24842831 PMCID: PMC4271056 DOI: 10.1093/infdis/jiu290

Abstract

Autophagy has been postulated to play role in mammalian host defense against fungal pathogens, although the molecular details remain unclear. Here, we show that primary macrophages deficient in the autophagic factor LC3 demonstrate diminished fungicidal activity but increased cytokine production in response to Candida albicans stimulation. LC3 recruitment to fungal phagosomes requires activation of the fungal pattern receptor dectin-1. LC3 recruitment to the phagosome also requires Syk signaling but is independent of all activity by Toll-like receptors and does not require the presence of the adaptor protein Card9. We further demonstrate that reactive oxygen species generation by NADPH oxidase is required for LC3 recruitment to the fungal phagosome. These observations directly link LC3 to the inflammatory pathway against C. albicans in macrophages.

© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].

Keywords: Candida albicans; LC3; NADPH oxidase; ROS; autophagy; dectin-1

References

  1. J Cell Sci. 2004 Jun 1;117(Pt 13):2805-12 - PubMed
  2. Immunity. 2005 Apr;22(4):507-17 - PubMed
  3. Nat Immunol. 2007 Jun;8(6):619-29 - PubMed
  4. Nat Immunol. 2011 Mar;12(3):222-30 - PubMed
  5. Proc Natl Acad Sci U S A. 2006 Oct 24;103(43):15945-50 - PubMed
  6. Ann N Y Acad Sci. 2008 Nov;1143:45-60 - PubMed
  7. Cell. 1997 Sep 5;90(5):939-49 - PubMed
  8. Autophagy. 2007 Nov-Dec;3(6):542-5 - PubMed
  9. Immunity. 2005 Oct;23(4):343-4 - PubMed
  10. Infect Immun. 2012 Sep;80(9):3065-76 - PubMed
  11. Integr Biol (Camb). 2012 Feb;4(2):220-7 - PubMed
  12. Nat Immunol. 2009 May;10(5):461-70 - PubMed
  13. J Biol Chem. 2000 Jun 30;275(26):20157-67 - PubMed
  14. Blood. 2005 Oct 1;106(7):2543-50 - PubMed
  15. J Immunol. 2009 Feb 15;182(4):2325-39 - PubMed
  16. Blood. 2010 Dec 9;116(24):5394-402 - PubMed
  17. Clin Microbiol Rev. 2007 Jan;20(1):133-63 - PubMed
  18. EMBO J. 2005 Mar 23;24(6):1277-86 - PubMed
  19. J Immunol. 2010 Dec 15;185(12):7614-22 - PubMed
  20. Science. 2012 Jun 8;336(6086):1314-7 - PubMed
  21. Free Radic Biol Med. 2012 Jul 1;53(1):72-80 - PubMed
  22. Autophagy. 2012 Apr;8(4):445-544 - PubMed
  23. J Biol Chem. 2013 May 31;288(22):16043-54 - PubMed
  24. Mol Biol Cell. 2008 Mar;19(3):797-806 - PubMed
  25. Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6226-31 - PubMed
  26. Antioxid Redox Signal. 2013 Feb 20;18(6):714-29 - PubMed
  27. Nature. 2007 Dec 20;450(7173):1253-7 - PubMed
  28. Nature. 2006 Aug 10;442(7103):651-6 - PubMed
  29. Nat Rev Immunol. 2006 Jan;6(1):33-43 - PubMed
  30. Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):16952-7 - PubMed
  31. Nat Genet. 2007 May;39(5):596-604 - PubMed
  32. J Infect Dis. 2007 Nov 15;196(10):1565-71 - PubMed
  33. J Biol Chem. 2012 Oct 5;287(41):34149-56 - PubMed
  34. Nature. 2007 Jan 4;445(7123):95-101 - PubMed
  35. Nat Cell Biol. 2007 Apr;9(4):367-78 - PubMed
  36. Nat Genet. 1995 Feb;9(2):202-9 - PubMed
  37. Autophagy. 2007 Sep-Oct;3(5):452-60 - PubMed
  38. Eur J Immunol. 2009 Feb;39(2):507-13 - PubMed
  39. EMBO J. 2007 Apr 4;26(7):1749-60 - PubMed
  40. Curr Opin Microbiol. 2011 Aug;14(4):392-9 - PubMed
  41. Nature. 2011 Jan 20;469(7330):323-35 - PubMed
  42. Cell. 2006 Jul 14;126(1):205-18 - PubMed
  43. J Exp Med. 2003 May 5;197(9):1107-17 - PubMed
  44. Infect Immun. 2011 Mar;79(3):1098-106 - PubMed
  45. J Exp Med. 2006 Aug 7;203(8):1915-25 - PubMed
  46. Ann N Y Acad Sci. 2012 Dec;1273:78-84 - PubMed
  47. Stem Cells. 2009 Mar;27(3):543-9 - PubMed
  48. N Engl J Med. 2009 Oct 29;361(18):1760-7 - PubMed

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