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Am J Respir Cell Mol Biol. 2016 Oct;55(4):521-531. doi: 10.1165/rcmb.2015-0291OC.

Repeated Mouse Lung Exposures to Stachybotrys chartarum Shift Immune Response from Type 1 to Type 2.

American journal of respiratory cell and molecular biology

Jamie H Rosenblum Lichtenstein, Ramon M Molina, Thomas C Donaghey, Yi-Hsiang H Hsu, Joel A Mathews, David I Kasahara, Jin-Ah Park, André Bordini, John J Godleski, Bruce S Gillis, Joseph D Brain

Affiliations

  1. 1 Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
  2. 2 Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, Massachusetts; and.
  3. 3 Department of Medicine, University of Illinois College of Medicine, Chicago, Illinois.

PMID: 27148627 PMCID: PMC5070103 DOI: 10.1165/rcmb.2015-0291OC

Abstract

After a single or multiple intratracheal instillations of Stachybotrys chartarum (S. chartarum or black mold) spores in BALB/c mice, we characterized cytokine production, metabolites, and inflammatory patterns by analyzing mouse bronchoalveolar lavage (BAL), lung tissue, and plasma. We found marked differences in BAL cell counts, especially large increases in lymphocytes and eosinophils in multiple-dosed mice. Formation of eosinophil-rich granulomas and airway goblet cell metaplasia were prevalent in the lungs of multiple-dosed mice but not in single- or saline-dosed groups. We detected changes in the cytokine expression profiles in both the BAL and plasma. Multiple pulmonary exposures to S. chartarum induced significant metabolic changes in the lungs but not in the plasma. These changes suggest a shift from type 1 inflammation after an acute exposure to type 2 inflammation after multiple exposures to S. chartarum. Eotaxin, vascular endothelial growth factor (VEGF), MIP-1α, MIP-1β, TNF-α, and the IL-8 analogs macrophage inflammatory protein-2 (MIP-2) and keratinocyte chemoattractant (KC), had more dramatic changes in multiple- than in single-dosed mice, and parallel the cytokines that characterize humans with histories of mold exposures versus unexposed control subjects. This repeated exposure model allows us to more realistically characterize responses to mold, such as cytokine, metabolic, and cellular changes.

Keywords: fungi; inflammation; lymphoid cells; macrophages; metabolome

References

  1. J Clin Invest. 1999 Aug;104(3):301-8 - PubMed
  2. Pediatr Allergy Immunol. 2013 Nov;24(7):697-703 - PubMed
  3. Front Biosci (Elite Ed). 2011 Jan 01;3:562-80 - PubMed
  4. Pediatrics. 2002 Sep;110(3):627-37 - PubMed
  5. J Nutr. 2004 Mar;134(3):489-92 - PubMed
  6. Shock. 2001 Apr;15(4):278-84 - PubMed
  7. Am J Physiol Lung Cell Mol Physiol. 2014 Mar 15;306(6):L508-20 - PubMed
  8. Mycopathologia. 2008 Feb;165(2):73-80 - PubMed
  9. Nucleic Acids Res. 2011 Jul;39(Web Server issue):W339-46 - PubMed
  10. Nature. 2011 Oct 05;478(7368):197-203 - PubMed
  11. Environ Res. 1976 Feb;11(1):13-33 - PubMed
  12. Proc Natl Acad Sci U S A. 1990 Jan;87(1):61-5 - PubMed
  13. Semin Immunopathol. 2015 Mar;37(2):107-16 - PubMed
  14. PLoS One. 2010 Nov 11;5(11):e13953 - PubMed
  15. Toxicol Sci. 2010 Jul;116(1):113-21 - PubMed
  16. Mycopathologia. 2007 Oct;164(4):171-81 - PubMed
  17. Nat Immunol. 2015 Feb;16(2):161-9 - PubMed
  18. Appl Environ Microbiol. 2005 Nov;71(11):7376-88 - PubMed
  19. J Exp Med. 1988 May 1;167(5):1737-42 - PubMed
  20. Front Immunol. 2014 Apr 01;5:142 - PubMed
  21. Curr Opin Immunol. 2013 Apr;25(2):156-60 - PubMed
  22. Immunity. 2014 Sep 18;41(3):366-74 - PubMed
  23. Int J Exp Pathol. 2008 Jun;89(3):201-8 - PubMed
  24. Toxicol Sci. 2002 Nov;70(1):98-109 - PubMed
  25. J Exp Med. 2001 Jan 15;193(2):255-61 - PubMed
  26. Curr Med Chem. 2016;23 (1):23-35 - PubMed
  27. Science. 2015 May 22;348(6237):aaa6566 - PubMed
  28. Am J Respir Cell Mol Biol. 2008 May;38(5):509-16 - PubMed
  29. J Toxicol Environ Health A. 2005 Aug 13;68(15):1321-35 - PubMed
  30. Am J Respir Cell Mol Biol. 2006 Oct;35(4):415-23 - PubMed
  31. Int Arch Allergy Immunol. 2011;155(1):74-85 - PubMed
  32. Mucosal Immunol. 2016 Jul;9(4):937-49 - PubMed
  33. Biochem Biophys Res Commun. 1993 Dec 30;197(3):1167-72 - PubMed
  34. Front Microbiol. 2015 Apr 21;6:344 - PubMed
  35. PLoS One. 2015 May 26;10(5):e0126926 - PubMed
  36. Nature. 1969 Aug 16;223(5207):742-5 - PubMed
  37. Immunology. 2011 Dec;134(4):448-58 - PubMed
  38. J Exp Med. 1994 Mar 1;179(3):881-7 - PubMed
  39. Cell Metab. 2012 Apr 4;15(4):432-7 - PubMed
  40. Toxicol Pathol. 2009 Jun;37(4):521-35 - PubMed
  41. J Allergy Clin Immunol. 1994 Jun;93(6):1013-20 - PubMed
  42. Inhal Toxicol. 2014 Jul;26(8):474-84 - PubMed
  43. Allergy. 2010 Feb;65(2):245-55 - PubMed
  44. Pediatrics. 2014 Nov;134 Suppl 3:S144 - PubMed
  45. Nat Med. 2014 Jan;20(1):54-61 - PubMed
  46. PLoS One. 2014 May 13;9(5):e97707 - PubMed
  47. J Allergy Clin Immunol. 2015 Sep;136(3):747-756.e4 - PubMed
  48. Annu Rev Physiol. 1992;54:303-29 - PubMed
  49. Z Rheumatol. 1991;50 Suppl 1:3-6 - PubMed
  50. Am J Respir Cell Mol Biol. 2016 Mar;54(3):331-40 - PubMed
  51. J Immunol. 2009 May 15;182(10):6418-25 - PubMed
  52. J Immunol. 2012 May 1;188(9):4558-67 - PubMed
  53. J Exp Med. 2014 Feb 10;211(2):199-208 - PubMed
  54. Mycopathologia. 2011 Jul;172(1):5-15 - PubMed
  55. J Immunol. 2013 Jan 1;190(1):349-56 - PubMed
  56. Toxicol Appl Pharmacol. 1982 Oct;66(1):9-29 - PubMed
  57. J Allergy Clin Immunol. 2015 Aug;136(2):312-22.e7 - PubMed
  58. Neurochem Res. 2009 Dec;34(12):2243-50 - PubMed
  59. Am J Respir Crit Care Med. 2006 Mar 1;173(5):512-8 - PubMed
  60. J Infect Dis. 2014 Aug 1;210(3):493-503 - PubMed
  61. Toxicol Sci. 2005 Apr;84(2):408-17 - PubMed
  62. J Immunol. 1999 Feb 15;162(4):2347-52 - PubMed
  63. Curr Allergy Asthma Rep. 2013 Jun;13(3):271-80 - PubMed
  64. J Clin Invest. 1999 Mar;103(6):779-88 - PubMed
  65. Am J Respir Cell Mol Biol. 2016 Jan;54(1):81-90 - PubMed

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