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Dermal exposure to the antimicrobial triclosan affects the gut microbiome and augments Th2 allergic responses mediated through Toll-like receptor 4

Nikki B Marshall, Ewa Lukomska, Carrie Mae Long and Stacey Anderson
J Immunol May 1, 2016, 196 (1 Supplement) 191.21;
Nikki B Marshall
1CDC
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Ewa Lukomska
1CDC
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Carrie Mae Long
2West Virginia Univ.
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Stacey Anderson
1CDC
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Abstract

Antimicrobial compounds like triclosan are ubiquitous in our environment; the CDC finds that75% of the general U.S. population has detectable levels in their urine. Curiously, recent epidemiological studies report positive associations between allergic disease and triclosan exposure. Our laboratory recently reported augmented allergic responses to ovalbumin in BALB/c mice with dermal triclosan exposure although triclosan itself was not immunogenic. Here we show that repeated application of triclosan to the skin alters expression of toll-like receptors including adramatic increase in TLR4 expression. In-vivo antibody-blockade of TLR4/MD2 significantly decreased responses in the skin tissue with triclosan exposure including expression of IL-6, TSLP, CXCL2, TLR2 and TLR4. The draining lymph nodes were also significantly affected by TLR4 blockade, including decreased cellularity and production of IL-4 and IL-13 by CD4 T cells. Proposed endogenous ligands of TLR4, S100A8 and S100A9, were also found to be highly expressed in the skin tissue and infiltrating neutrophils thus identifying a possible mechanism of TLR4 activation. Changes in gut microbiome have also been linked to changes in Th2 allergic responses. Here we found that after 28 days of topical application of triclosan, the relative abundance of Lactobacillus was increased in the gut. A specific mechanism of action of triclosan is inhibition of the enoyl-ACP reductase FabI gene involved in bacterial fatty acid synthesis which is not expressed by Lactobacillus. Together these data suggest that triclosan could augment allergic responses in part through activation of the TLR4 pathway and modulating the host microbiome.

  • Copyright © 2016 by The American Association of Immunologists, Inc.
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The Journal of Immunology
Vol. 196, Issue 1 Supplement
1 May 2016
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Dermal exposure to the antimicrobial triclosan affects the gut microbiome and augments Th2 allergic responses mediated through Toll-like receptor 4
Nikki B Marshall, Ewa Lukomska, Carrie Mae Long, Stacey Anderson
The Journal of Immunology May 1, 2016, 196 (1 Supplement) 191.21;

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Dermal exposure to the antimicrobial triclosan affects the gut microbiome and augments Th2 allergic responses mediated through Toll-like receptor 4
Nikki B Marshall, Ewa Lukomska, Carrie Mae Long, Stacey Anderson
The Journal of Immunology May 1, 2016, 196 (1 Supplement) 191.21;
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Print ISSN 0022-1767        Online ISSN 1550-6606