Acinetobacter baumannii 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
Acinetobacter baumannii. Wild-type (WT) and
CRAMP knockout mice were infected intranasally with the
bacteria.
CRAMP−/−
mice exhibited increased bacterial
colony-forming units (CFUs) in
bronchoalveolar lavage (BAL) fluid after A. baumannii
infection 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
CRAMP−/−
mice compared to WT
mice 1 day after
infection. In an
in vitro assay using thioglycollate-induced peritoneal
neutrophils, the
ability of bacterial
phagocytosis and
killing was impaired in
CRAMP−/−
neutrophils compared to the WT
cells.
CRAMP was also essential for the
production of
cytokines and
chemokines in response to A. baumannii in
neutrophils. In addition, the A. baumannii-induced inhibitor of κB-α degradation and
phosphorylation of
p38 MAPK were impaired in
CRAMP−/−
neutrophils, whereas ERK and JNK
phosphorylation was upregulated. Our results indicate that
CRAMP plays an important
role in the host defense against pulmonary
infection with A. baumannii by promoting the antibacterial activity of
neutrophils and regulating the
innate immune responses.