Topical Application of the Anti-Microbial Chemical Triclosan Induces Immunomodulatory Responses Through the S100A8/A9-TLR4 Pathway

Details

• Personal Author:
  Anderson, Stacey E. ; Hettick JM ; Long CM ; Lukomska E ; Marshall NB ; Nayak, Ajay P.
• Description:
  The anti-microbial compound triclosan is incorporated into numerous consumer products and is detectable in the urine of 75% of the general United States population. Recent epidemiological studies report positive associations with urinary triclosan levels and allergic disease. Although not sensitizing, earlier studies previously found that repeated topical application of triclosan augments the allergic response to ovalbumin (OVA) though a thymic stromal lymphopoietin (TSLP) pathway in mice. In the present study, early immunological effects following triclosan exposure were further evaluated following topical application in a murine model. These investigations revealed abundant expression of S100A8/A9, which reportedly acts as an endogenous ligand for Toll-like Receptor 4 (TLR4), in skin tissues and in infiltrating leukocytes during topical application of 0.75-3.0% triclosan. Expression of Tlr4 along with Tlr1, Tlr2 and Tlr6 increased in skin tissues over time with triclosan exposure; high levels of TLR4 were expressed on skin-infiltrating leukocytes. In vivo antibody blockade of the TLR4/MD-2 receptor complex impaired local inflammatory responses after four days, as evidenced by decreased Il6, Tnfa, S100a8, S100a9, Tlr1, Tlr2, Tlr4 and Tlr6 expression in the skin and decreased lymph node cellularity and production of IL-4 and IL-13 by lymph node T-cells. After nine days of triclosan exposure with TLR4/MD-2 blockade, impaired T-helper cell type 2 (TH2) cytokine responses were sustained, but other early effects on skin and lymph node cellularity were lost; this suggested alternative ligands/receptors compensated for the loss of TLR4 signaling. Taken together, these data suggest the S100A8/A9-TLR4 pathway plays an early role in augmenting immunomodulatory responses with triclosan exposure and support a role for the innate immune system in chemical adjuvancy. [Description provided by NIOSH]
• Subjects:
  Antibodies Hypersensitivity Immune System Laboratories Occupational Health Safety
• Keywords:
  Allergic Reactions Antimicrobials Author Keywords: Triclosan Cytokines Dose Response Immunochemistry Immunomodulation Innate Immunity In Vivo Study Laboratory Animals TLR4

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• ISSN:
  1547-691X
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  50-59
• Volume:
  14
• Issue:
  1
• NIOSHTIC Number:
  nn:20050203
• Citation:
  J Immunotoxicol 2017 Jan; 14(1):50-59
• Contact Point Address:
  Stacey E. Anderson, Allergy and Clinical Immunology Branch, CDC-NIOSH, 1095 Willowdale Road, m/s 4020, Morgantown, WV 26505, USA
• Email:
  sanderson4@cdc.gov
• CAS Registry Number:
  Triclosan (CAS RN 3380-34-5)
• Federal Fiscal Year:
  2017
• NORA Priority Area:
  Healthcare and Social Assistance ; Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Immunotoxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:fa6d9e0b2d2ad4c317b083a6c9098cd409218e70120f927bc90fe958d834851451d5e9898018907258ab0bdba577e03394c04832448724ff447f41ea77c57c7f
• Download URL:
  https://stacks.cdc.gov/view/cdc/210651/cdc_210651_DS1.pdf
• File Type:
  [PDF - 1.67 MB ]