Cathelicidin-related Antimicrobial Peptide Contributes to Host Immune Responses Against Pulmonary Infection within Mice.

is known for its multidrug antibiotic resistance. New approaches to treating drug-resistant bacterial infections are urgently required. Cathelicidin-related antimicrobial peptide (CRAMP) is a murine antimicrobial peptide that exerts diverse immune functions, including both direct bacterial cell killing and immunomodulatory effects. In this study, we sought to identify the role of CRAMP in the host immune response to multidrug-resistant. Wild-type (WT) and CRAMP knockout mice were infected intranasally with the bacteria. CRAMPmice exhibited increased bacterial colony-forming units (CFUs) in bronchoalveolar lavage (BAL) fluid afterinfection compared to WT mice. The loss of CRAMP expression resulted in a significant decrease in the recruitment of immune cells, primarily neutrophils. The levels of IL-6 and CXCL1 were lower, whereas the levels of IL-10 were significantly higher in the BAL fluid of CRAMPmice compared to WT mice 1 day after infection. In anassay using thioglycollate-induced peritoneal neutrophils, the ability of bacterial phagocytosis and killing was impaired in CRAMPneutrophils compared to the WT cells. CRAMP was also essential for the production of cytokines and chemokines in response toin neutrophils. In addition, the-induced inhibitor of κB-α degradation and phosphorylation of p38 MAPK were impaired in CRAMPneutrophils, whereas ERK and JNK phosphorylation was upregulated. Our results indicate that CRAMP plays an important role in the host defense against pulmonary infection withby promoting the antibacterial activity of neutrophils and regulating the innate immune responses.