PMID- 27315768
OWN - NLM
STAT- MEDLINE
DCOM- 20170803
LR  - 20181107
IS  - 1097-6825 (Electronic)
IS  - 0091-6749 (Linking)
VI  - 139
IP  - 2
DP  - 2017 Feb
TI  - Staphylococcal serine protease-like proteins are pacemakers of allergic airway 
      reactions to Staphylococcus aureus.
PG  - 492-500.e8
LID - S0091-6749(16)30272-X [pii]
LID - 10.1016/j.jaci.2016.03.045 [doi]
AB  - BACKGROUND: A substantial subgroup of asthmatic patients have "nonallergic" or 
      idiopathic asthma, which often takes a severe course and is difficult to treat. 
      The cause might be allergic reactions to the gram-positive pathogen 
      Staphylococcus aureus, a frequent colonizer of the upper airways. However, the 
      driving allergens of S aureus have remained elusive. OBJECTIVE: We sought to 
      search for potentially allergenic S aureus proteins and characterize the immune 
      response directed against them. METHODS: S aureus extracellular proteins targeted 
      by human serum IgG(4) were identified by means of immunoblotting to screen for 
      potential bacterial allergens. Candidate antigens were expressed as recombinant 
      proteins and used to analyze the established cellular and humoral immune 
      responses in healthy adults and asthmatic patients. The ability to induce a type 
      2 immune response in vivo was tested in a mouse asthma model. RESULTS: We 
      identified staphylococcal serine protease-like proteins (Spls) as dominant 
      IgG(4)-binding S aureus proteins. SplA through SplF are extracellular proteases 
      of unknown function expressed by S aureus in vivo. Spls elicited IgE antibody 
      responses in most asthmatic patients. In healthy S aureus carriers and 
      noncarriers, peripheral blood T cells elaborated T(H)2 cytokines after 
      stimulation with Spls, as is typical for allergens. In contrast, T(H)1/T(H)17 
      cytokines, which dominated the response to S aureus alpha-hemolysin, were of low 
      concentration or absent. In mice inhalation of SplD without adjuvant induced lung 
      inflammation characterized by T(H)2 cytokines and eosinophil infiltration. 
      CONCLUSION: We identify Spls as triggering allergens released by S aureus, 
      opening prospects for diagnosis and causal therapy of asthma.
CI  - Copyright (c) 2016 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Stentzel, Sebastian
AU  - Stentzel S
AD  - Department of Immunology, University Medicine Greifswald, Greifswald, Germany.
FAU - Teufelberger, Andrea
AU  - Teufelberger A
AD  - Upper Airways Research Laboratory, Ghent University, Ghent, Belgium.
FAU - Nordengrun, Maria
AU  - Nordengrun M
AD  - Department of Immunology, University Medicine Greifswald, Greifswald, Germany.
FAU - Kolata, Julia
AU  - Kolata J
AD  - Department of Immunology, University Medicine Greifswald, Greifswald, Germany; 
      Medical Microbiology, University Medical Center Utrecht, Utrecht, The 
      Netherlands.
FAU - Schmidt, Frank
AU  - Schmidt F
AD  - Interfaculty Institute for Genetics and Functional Genomics, Department of 
      Functional Genomics, University Medicine Greifswald, Greifswald, Germany; Junior 
      Group Applied Proteomics, ZIK FunGene, University Medicine Greifswald, 
      Greifswald, Germany.
FAU - van Crombruggen, Koen
AU  - van Crombruggen K
AD  - Upper Airways Research Laboratory, Ghent University, Ghent, Belgium.
FAU - Michalik, Stephan
AU  - Michalik S
AD  - Interfaculty Institute for Genetics and Functional Genomics, Department of 
      Functional Genomics, University Medicine Greifswald, Greifswald, Germany; Junior 
      Group Applied Proteomics, ZIK FunGene, University Medicine Greifswald, 
      Greifswald, Germany.
FAU - Kumpfmuller, Jana
AU  - Kumpfmuller J
AD  - Department of Pharmaceutical Biotechnology, Institute of Pharmacy, 
      Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany; Department of 
      Biomolecular Chemistry, Leibniz Institute for Natural Product Research and 
      Infection Biology, HKI, Jena, Germany.
FAU - Tischer, Sebastian
AU  - Tischer S
AD  - Department of Immunology, University Medicine Greifswald, Greifswald, Germany.
FAU - Schweder, Thomas
AU  - Schweder T
AD  - Department of Pharmaceutical Biotechnology, Institute of Pharmacy, 
      Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.
FAU - Hecker, Michael
AU  - Hecker M
AD  - Institute for Microbiology, Ernst-Moritz-Arndt-University Greifswald, Greifswald, 
      Germany.
FAU - Engelmann, Susanne
AU  - Engelmann S
AD  - Institute for Microbiology, Ernst-Moritz-Arndt-University Greifswald, Greifswald, 
      Germany; Institute for Microbiology, University of Braunschweig, Braunschweig, 
      Germany; Helmholtz Center for Infection Research, Microbial Proteomics, 
      Braunschweig, Germany.
FAU - Volker, Uwe
AU  - Volker U
AD  - Interfaculty Institute for Genetics and Functional Genomics, Department of 
      Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
FAU - Krysko, Olga
AU  - Krysko O
AD  - Upper Airways Research Laboratory, Ghent University, Ghent, Belgium.
FAU - Bachert, Claus
AU  - Bachert C
AD  - Upper Airways Research Laboratory, Ghent University, Ghent, Belgium; Division of 
      Ear, Nose, and Throat Diseases, Clintec, Karolinska Institute, Stockholm, Sweden.
FAU - Broker, Barbara M
AU  - Broker BM
AD  - Department of Immunology, University Medicine Greifswald, Greifswald, Germany. 
      Electronic address: broeker@uni-greifswald.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160510
PL  - United States
TA  - J Allergy Clin Immunol
JT  - The Journal of allergy and clinical immunology
JID - 1275002
RN  - 0 (Allergens)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Immunoglobulin G)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - EC 3.4.- (Serine Proteases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Allergens/immunology/*metabolism
MH  - Animals
MH  - Asthma/*immunology
MH  - Bacterial Proteins/immunology/*metabolism
MH  - Cells, Cultured
MH  - Female
MH  - Humans
MH  - Hypersensitivity/*immunology
MH  - Immunoglobulin E/metabolism
MH  - Immunoglobulin G/metabolism
MH  - Lymphocyte Activation
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Middle Aged
MH  - Protein Binding
MH  - Serine Proteases/*immunology
MH  - Staphylococcal Infections/*immunology
MH  - Staphylococcus aureus/*immunology
MH  - Th2 Cells/*immunology
MH  - Young Adult
OTO - NOTNLM
OT  - Asthma
OT  - IgE
OT  - Staphylococcus aureus
OT  - serine protease-like proteins
OT  - type 2 inflammation
EDAT- 2016/06/19 06:00
MHDA- 2017/08/05 06:00
CRDT- 2016/06/19 06:00
PHST- 2015/10/04 00:00 [received]
PHST- 2016/02/15 00:00 [revised]
PHST- 2016/03/22 00:00 [accepted]
PHST- 2016/06/19 06:00 [pubmed]
PHST- 2017/08/05 06:00 [medline]
PHST- 2016/06/19 06:00 [entrez]
AID - S0091-6749(16)30272-X [pii]
AID - 10.1016/j.jaci.2016.03.045 [doi]
PST - ppublish
SO  - J Allergy Clin Immunol. 2017 Feb;139(2):492-500.e8. doi: 
      10.1016/j.jaci.2016.03.045. Epub 2016 May 10.