Cathelicidin-related antimicrobial peptide contributes to host immune responses against pulmonary infection with Acinetobacter baumannii in mice

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Title
Cathelicidin-related antimicrobial peptide contributes to host immune responses against pulmonary infection with Acinetobacter baumannii in mice
Author(s)
M J Kang; A R Jang; J Y Park; J H Ahn; T S Lee; D Y Kim; D H Jung; E J Song; Jung Joo Hong; J H Park
Bibliographic Citation
Immune Network, vol. 20, no. 3, pp. e25-e25
Publication Year
2020
Abstract
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.
Keyword
Acinetobacter baumanniiCRAMPNeutrophilsInnate immune response
ISSN
I000-0135
Publisher
South Korea
DOI
http://dx.doi.org/10.4110/in.2020.20.e25
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > National Primate Research Center > 1. Journal Articles
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