title: Commensal bacteria lipoteichoic acid increases skin mast cell antimicrobial activity against vaccinia viruses.
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.
authors: Division of Dermatology, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
authors: Zhenping
authors: Z
authors: Wang
authors: Daniel T
authors: DT
authors: MacLeod
authors: Anna
authors: A
authors: Di Nardo
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000276:immunology; D005434:Flow Cytometry; D006094:Gram-Positive Bacteria / Q000502:physiology; D015151:Immunoblotting; D008070:Lipopolysaccharides / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D012867:Skin / Q000276:immunology* / Q000382:microbiology*; D013682:Teichoic Acids / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology; D014615:Vaccinia / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D008070:Lipopolysaccharides; D013682:Teichoic Acids; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; C009900:lipoteichoic acid