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Killing of Pseudomonas aeruginosa by Chicken Cathelicidin-2 Is Immunogenically Silent, Preventing Lung Inflammation In Vivo.

ABSTRACT The development of antibiotic resistance by Pseudomonas aeruginosa is a major concern in the treatment of bacterial pneumonia. In the search for novel anti-infective therapies, the chicken-derived peptide cathelicidin-2 (CATH-2) has emerged as a potential candidate, with strong broad-spectr... Full description

Journal Title: Infection and immunity December 2017, Vol.85(12)
Main Author: Coorens, Maarten
Other Authors: Banaschewski, Brandon J H , Baer, Brandon J , Yamashita, Cory , van Dijk, Albert , Haagsman, Henk P , Veldhuizen, Ruud A W , Veldhuizen, Edwin J A
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1098-5522 ; DOI: 10.1128/IAI.00546-17
Link: http://search.proquest.com/docview/1943285389/?pq-origsite=primo
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title: Killing of Pseudomonas aeruginosa by Chicken Cathelicidin-2 Is Immunogenically Silent, Preventing Lung Inflammation In Vivo.
format: Article
creator:
  • Coorens, Maarten
  • Banaschewski, Brandon J H
  • Baer, Brandon J
  • Yamashita, Cory
  • van Dijk, Albert
  • Haagsman, Henk P
  • Veldhuizen, Ruud A W
  • Veldhuizen, Edwin J A
subjects:
  • Animals–Immunology
  • Antimicrobial Cationic Peptides–Pharmacology
  • Cell Line–Immunology
  • Chemokines–Immunology
  • Chickens–Immunology
  • Cytokines–Immunology
  • Disease Models, Animal–Prevention & Control
  • Immunity, Innate–Immunology
  • Inflammation–Microbiology
  • Lung–Immunology
  • Macrophages–Microbiology
  • Male–Immunology
  • Mice–Prevention & Control
  • Mice, Inbred C57bl–Immunology
  • Neutrophil Infiltration–Veterinary
  • Pneumonia, Bacterial–Drug Effects
  • Pseudomonas Infections–Drug Effects
  • Pseudomonas Aeruginosa–Drug Effects
  • Antimicrobial Cationic Peptides
  • Cmap27 Protein, Chicken
  • Chemokines
  • Cytokines
  • Alternative to Antibiotics
  • Cathelicidin
  • Host Defense Peptide
  • Immunomodulation
  • Innate Immunity
ispartof: Infection and immunity, December 2017, Vol.85(12)
description: ABSTRACT The development of antibiotic resistance by Pseudomonas aeruginosa is a major concern in the treatment of bacterial pneumonia. In the search for novel anti-infective therapies, the chicken-derived peptide cathelicidin-2 (CATH-2) has emerged as a potential candidate, with strong broad-spectrum antimicrobial activity and the ability to limit inflammation by inhibiting Toll-like receptor 2 (TLR2) and TLR4 activation. However, as it is unknown how CATH-2 affects inflammation in vivo , we investigated how CATH-2-mediated killing of P. aeruginosa affects lung inflammation in a murine model. First, murine macrophages were used to determine whether CATH-2-mediated killing of P. aeruginosa reduced proinflammatory cytokine production in vitro . Next, a murine lung model was used to analyze how CATH-2-mediated killing of P. aeruginosa affects neutrophil and macrophage recruitment as well as cytokine/chemokine production in the lung. Our results show that CATH-2 kills P. aeruginosa in an immunogenically silent manner both in vitro and in vivo . Treatment with CATH-2-killed P. aeruginosa showed reduced neutrophil recruitment to the lung as well as inhibition of cytokine and chemokine production, compared to treatment with heat- or gentamicin-killed bacteria. Together, these results show the potential for CATH-2 as a dual-activity antibiotic in bacterial pneumonia, which can both kill P. aeruginosa and prevent excessive inflammation.
language: eng
source:
identifier: E-ISSN: 1098-5522 ; DOI: 10.1128/IAI.00546-17
fulltext: fulltext
issn:
  • 10985522
  • 1098-5522
url: Link


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titleKilling of Pseudomonas aeruginosa by Chicken Cathelicidin-2 Is Immunogenically Silent, Preventing Lung Inflammation In Vivo.
creatorCoorens, Maarten ; Banaschewski, Brandon J H ; Baer, Brandon J ; Yamashita, Cory ; van Dijk, Albert ; Haagsman, Henk P ; Veldhuizen, Ruud A W ; Veldhuizen, Edwin J A
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ispartofInfection and immunity, December 2017, Vol.85(12)
identifierE-ISSN: 1098-5522 ; DOI: 10.1128/IAI.00546-17
subjectAnimals–Immunology ; Antimicrobial Cationic Peptides–Pharmacology ; Cell Line–Immunology ; Chemokines–Immunology ; Chickens–Immunology ; Cytokines–Immunology ; Disease Models, Animal–Prevention & Control ; Immunity, Innate–Immunology ; Inflammation–Microbiology ; Lung–Immunology ; Macrophages–Microbiology ; Male–Immunology ; Mice–Prevention & Control ; Mice, Inbred C57bl–Immunology ; Neutrophil Infiltration–Veterinary ; Pneumonia, Bacterial–Drug Effects ; Pseudomonas Infections–Drug Effects ; Pseudomonas Aeruginosa–Drug Effects ; Antimicrobial Cationic Peptides ; Cmap27 Protein, Chicken ; Chemokines ; Cytokines ; Alternative to Antibiotics ; Cathelicidin ; Host Defense Peptide ; Immunomodulation ; Innate Immunity
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descriptionABSTRACT The development of antibiotic resistance by Pseudomonas aeruginosa is a major concern in the treatment of bacterial pneumonia. In the search for novel anti-infective therapies, the chicken-derived peptide cathelicidin-2 (CATH-2) has emerged as a potential candidate, with strong broad-spectrum antimicrobial activity and the ability to limit inflammation by inhibiting Toll-like receptor 2 (TLR2) and TLR4 activation. However, as it is unknown how CATH-2 affects inflammation in vivo , we investigated how CATH-2-mediated killing of P. aeruginosa affects lung inflammation in a murine model. First, murine macrophages were used to determine whether CATH-2-mediated killing of P. aeruginosa reduced proinflammatory cytokine production in vitro . Next, a murine lung model was used to analyze how CATH-2-mediated killing of P. aeruginosa affects neutrophil and macrophage recruitment as well as cytokine/chemokine production in the lung. Our results show that CATH-2 kills P. aeruginosa in an immunogenically silent manner both in vitro and in vivo . Treatment with CATH-2-killed P. aeruginosa showed reduced neutrophil recruitment to the lung as well as inhibition of cytokine and chemokine production, compared to treatment with heat- or gentamicin-killed bacteria. Together, these results show the potential for CATH-2 as a dual-activity antibiotic in bacterial pneumonia, which can both kill P. aeruginosa and prevent excessive inflammation.
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