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

• Published in: Infection and immunity Vol. 85; no. 12
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01-12-2017
• Subjects: Host Response and Inflammation; Spotlight; host defense peptide; immunomodulation; alternative to antibiotics; cathelicidin; innate immunity
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00546-17

The development of antibiotic resistance by
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
, we investigated how CATH-2-mediated killing of
affects lung inflammation in a murine model. First, murine macrophages were used to determine whether CATH-2-mediated killing of
reduced proinflammatory cytokine production
Next, a murine lung model was used to analyze how CATH-2-mediated killing of
affects neutrophil and macrophage recruitment as well as cytokine/chemokine production in the lung. Our results show that CATH-2 kills
in an immunogenically silent manner both
and
Treatment with CATH-2-killed
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
and prevent excessive inflammation.