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

The development of antibiotic resistance byis 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 ofaffects lung inflammation in a murine model. First, murine macrophages were used to determine whether CATH-2-mediated killing ofreduced proinflammatory cytokine productionNext, a murine lung model was used to analyze how CATH-2-mediated killing ofaffects neutrophil and macrophage recruitment as well as cytokine/chemokine production in the lung. Our results show that CATH-2 killsin an immunogenically silent manner bothandTreatment with CATH-2-killedshowed 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 killand prevent excessive inflammation.