title: Delta Hemolysin and Phenol-Soluble Modulins, but Not Alpha Hemolysin or Panton-Valentine Leukocidin, Induce Mast Cell Activation.
abstract: Mast cells are located at host interfaces, such as the skin, and contribute to the first-line defense against pathogens by releasing soluble mediators, including those that induce itching and scratching behavior. Here, we show that delta-hemolysin (Hld) and phenol soluble modulins (PSMs) PSMα1 and PSMα3, but not alpha-hemolysin (Hla) or Panton-Valentine leukocidin (PVL), induce dose-dependent tryptase, and lactate dehydrogenase (LDH) release by the HMC-1 human mast cell line. Using supernatants from isogenic strains, we verified that tryptase and LDH release was Hld- and PSMα-dependent. PSMα1 and Hld production was detected in 65 and 17% of humanStaphylococcus aureus-infected skin abscess specimens, respectively, but they were producedin vitroby all clinical isolates. The results suggest that Hld and PSM-α1 producedin vivoduringS. aureusskin infections induce the release of mast cell mediators responsible for itching and scratching behavior, which may enhance skin to skin transmission ofS. aureus viathe hands. As Hld and PSMs are upregulated by accessory gene regulator (agr), their association may contribute to the elective transmission ofS. aureusstrains with a functional agr system.
authors.affiliation: Centre International de Recherche en Infectiologie, Institut National de la Santé et de la Recherche Médicale U1111, Université Lyon 1, Centre National de la Recherche Scientifique UMR5308, Ecole Normale Supérieure de LyonLyon, France; Hospices Civils de LyonLyon, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Hodille
authors.affiliation: Hospices Civils de LyonLyon, France; Laboratoire de Biochimie, Centre de Biologie SudLyon, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Cuerq
authors.affiliation: Centre International de Recherche en Infectiologie, Institut National de la Santé et de la Recherche Médicale U1111, Université Lyon 1, Centre National de la Recherche Scientifique UMR5308, Ecole Normale Supérieure de Lyon Lyon, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Badiou
authors.affiliation: Hospices Civils de LyonLyon, France; Laboratoire d'Immunologie, Centre de Biologie SudLyon, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Bienvenu
authors.affiliation: Hospices Civils de LyonLyon, France; Laboratoire de Biochimie, Centre de Biologie SudLyon, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Steghens
authors.affiliation: Hospices Civils de LyonLyon, France; Laboratoire de Biochimie, Groupement Hospitalier EstLyon, France.
authors.forename: Régine
authors.initials: R
authors.lastname: Cartier
authors.affiliation: Centre International de Recherche en Infectiologie, Institut National de la Santé et de la Recherche Médicale U1111, Université Lyon 1, Centre National de la Recherche Scientifique UMR5308, Ecole Normale Supérieure de LyonLyon, France; Hospices Civils de LyonLyon, France; Centre National de Référence des StaphylocoquesBron, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Bes
authors.affiliation: Centre International de Recherche en Infectiologie, Institut National de la Santé et de la Recherche Médicale U1111, Université Lyon 1, Centre National de la Recherche Scientifique UMR5308, Ecole Normale Supérieure de LyonLyon, France; Hospices Civils de LyonLyon, France; Centre National de Référence des StaphylocoquesBron, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Tristan
authors.affiliation: Hospices Civils de LyonLyon, France; Laboratoire d'hématologie, Centre de Biologie SudLyon, France.
authors.forename: Adriana
authors.initials: A
authors.lastname: Plesa
authors.affiliation: Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, University of California San Francisco, CA, USA.
authors.forename: Vien T M
authors.initials: VT
authors.lastname: Le
authors.affiliation: Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, University of California San Francisco, CA, USA.
authors.forename: Binh A
authors.initials: BA
authors.lastname: Diep
authors.affiliation: Centre International de Recherche en Infectiologie, Institut National de la Santé et de la Recherche Médicale U1111, Université Lyon 1, Centre National de la Recherche Scientifique UMR5308, Ecole Normale Supérieure de LyonLyon, France; Hospices Civils de LyonLyon, France; Centre National de Référence des StaphylocoquesBron, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Lina
authors.affiliation: Centre International de Recherche en Infectiologie, Institut National de la Santé et de la Recherche Médicale U1111, Université Lyon 1, Centre National de la Recherche Scientifique UMR5308, Ecole Normale Supérieure de LyonLyon, France; Hospices Civils de LyonLyon, France; Centre National de Référence des StaphylocoquesBron, France.
authors.forename: Oana
authors.initials: O
authors.lastname: Dumitrescu
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D005098:Exotoxins / Q000378:metabolism / Q000494:pharmacology*; D006460:Hemolysin Proteins / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007956:Leukocidins / Q000378:metabolism / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D010088:Oxidoreductases / Q000378:metabolism; D011537:Pruritus / Q000276:immunology / Q000382:microbiology; D013207:Staphylococcal Skin Infections / Q000378:metabolism / Q000503:physiopathology*; D013211:Staphylococcus aureus / Q000302:isolation & purification / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D053802:Tryptases / Q000378:metabolism; D015854:Up-Regulation; D037521:Virulence Factors
chemical_list: C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D005098:Exotoxins; D006460:Hemolysin Proteins; D007956:Leukocidins; C078284:Panton-Valentine leukocidin; D015534:Trans-Activators; D037521:Virulence Factors; C025971:staphylococcal delta toxin; C025994:delta hemolysin protein, Staphylococcus aureus; D010088:Oxidoreductases; D053802:Tryptases
keywords: Staphylococcus aureus; accessory gene regulator; delta hemolysin; hand-transmission; mast cells; phenol-soluble modulins; virulence