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Commensal Bacteria Lipoteichoic Acid Increases Skin Mast Cell Antimicrobial Activity against Vaccinia Viruses

Zhenping Wang, Daniel T. MacLeod and Anna Di Nardo
J Immunol August 15, 2012, 189 (4) 1551-1558; DOI: https://doi.org/10.4049/jimmunol.1200471
Zhenping Wang
Division of Dermatology, Department of Medicine, University of California San Diego, La Jolla, CA 92093
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Daniel T. MacLeod
Division of Dermatology, Department of Medicine, University of California San Diego, La Jolla, CA 92093
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Anna Di Nardo
Division of Dermatology, Department of Medicine, University of California San Diego, La Jolla, CA 92093
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Abstract

Mast cells (MCs) are considered sentinels in the skin and mucosa. Their ability to release antimicrobial peptides, such as cathelicidin, protects against bacterial infections when the epithelial barrier is breached. We recently described that MCs defend against bacterial and viral infections through the release of cathelicidin during degranulation. In this study, we hypothesize that cathelicidin expression is induced in MCs by the activation of TLR2 from bacterial products (lipoteichoic acid) produced by commensal bacteria at the epithelial surface. Our research shows that signaling through TLR2 increases the production and expression of cathelicidin in mast cells, thereby enhancing their capacity to fight vaccinia virus. MCs deficient in cathelicidin were less efficient in killing vaccinia virus after lipoteichoic acid stimulation than wild-type cells. Moreover, the activation of TLR2 increases the MC recruitment at the skin barrier interface. Taken together, our findings reveal that the expression and control of antimicrobial peptides and TLR signaling on MCs are key in fighting viral infection. Our findings also provide new insights into the pathogenesis of skin infections and suggest potential roles for MCs and TLR2 ligands in antiviral therapy.

Footnotes

  • This work was supported by National Institutes of Health-National Institute of Allergy and Infectious Diseases Grants 1R21A1074766-01A2 and 1R01AI093957 (to A.D.N.).

  • Abbreviations used in this article:

    AMP
    antimicrobial peptide
    LTA
    lipoteichoic acid
    LTA-SE
    Staphylococcus epidermidis LTA
    MC
    mast cell
    MOI
    multiple of infection
    VV
    vaccinia virus.

  • Received February 8, 2012.
  • Accepted June 5, 2012.
  • Copyright © 2012 by The American Association of Immunologists, Inc.
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The Journal of Immunology: 189 (4)
The Journal of Immunology
Vol. 189, Issue 4
15 Aug 2012
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Commensal Bacteria Lipoteichoic Acid Increases Skin Mast Cell Antimicrobial Activity against Vaccinia Viruses
Zhenping Wang, Daniel T. MacLeod, Anna Di Nardo
The Journal of Immunology August 15, 2012, 189 (4) 1551-1558; DOI: 10.4049/jimmunol.1200471

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Commensal Bacteria Lipoteichoic Acid Increases Skin Mast Cell Antimicrobial Activity against Vaccinia Viruses
Zhenping Wang, Daniel T. MacLeod, Anna Di Nardo
The Journal of Immunology August 15, 2012, 189 (4) 1551-1558; DOI: 10.4049/jimmunol.1200471
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