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Infect Immun. 2017 Nov 17;85(12). pii: e00546-17. doi: 10.1128/IAI.00546-17. Print 2017 Dec.

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

Author information

1
Department of Infectious Diseases and Immunology, Division of Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
2
Department of Physiology and Pharmacology, the University of Western Ontario, London, Ontario, Canada.
3
Department of Infectious Diseases and Immunology, Division of Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands H.P.Haagsman@uu.nl.

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.

KEYWORDS:

alternative to antibiotics; cathelicidin; host defense peptide; immunomodulation; innate immunity

PMID:
28947647
PMCID:
PMC5695126
DOI:
10.1128/IAI.00546-17
[Indexed for MEDLINE]
Free PMC Article

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