PMID- 32655973 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 1598-2629 (Print) IS - 2092-6685 (Electronic) IS - 1598-2629 (Linking) VI - 20 IP - 3 DP - 2020 Jun TI - Cathelicidin-related Antimicrobial Peptide Contributes to Host Immune Responses Against Pulmonary Infection with Acinetobacter baumannii in Mice. PG - e25 LID - 10.4110/in.2020.20.e25 [doi] LID - e25 AB - 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 kappaB-alpha 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. CI - Copyright (c) 2020. The Korean Association of Immunologists. FAU - Kang, Min-Jung AU - Kang MJ AD - Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, Korea. FAU - Jang, Ah-Ra AU - Jang AR AUID- ORCID: 0000-0003-2378-5720 AD - Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, Korea. FAU - Park, Ji-Yeon AU - Park JY AD - Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, Korea. FAU - Ahn, Jae-Hun AU - Ahn JH AUID- ORCID: 0000-0003-4545-1211 AD - Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, Korea. FAU - Lee, Tae-Sung AU - Lee TS AD - Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, Korea. FAU - Kim, Dong-Yeon AU - Kim DY AD - Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, Korea. FAU - Jung, Do-Hyeon AU - Jung DH AD - Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, Korea. FAU - Song, Eun-Jung AU - Song EJ AUID- ORCID: 0000-0002-1495-488X AD - Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, Korea. FAU - Hong, Jung Joo AU - Hong JJ AUID- ORCID: 0000-0002-9795-6513 AD - National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk 28116, Korea. FAU - Park, Jong-Hwan AU - Park JH AUID- ORCID: 0000-0003-4664-5640 AD - Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, Korea. LA - eng PT - Journal Article DEP - 20200520 PL - Korea (South) TA - Immune Netw JT - Immune network JID - 101137270 PMC - PMC7327154 OTO - NOTNLM OT - Acinetobacter baumannii OT - CRAMP OT - Innate immune response OT - Neutrophils COIS- Conflicts of Interest: The authors declare no potential conflicts of interest. EDAT- 2020/07/14 06:00 MHDA- 2020/07/14 06:01 PMCR- 2020/06/01 CRDT- 2020/07/14 06:00 PHST- 2020/01/08 00:00 [received] PHST- 2020/04/27 00:00 [revised] PHST- 2020/05/06 00:00 [accepted] PHST- 2020/07/14 06:00 [entrez] PHST- 2020/07/14 06:00 [pubmed] PHST- 2020/07/14 06:01 [medline] PHST- 2020/06/01 00:00 [pmc-release] AID - 2020200306 [pii] AID - 10.4110/in.2020.20.e25 [doi] PST - epublish SO - Immune Netw. 2020 May 20;20(3):e25. doi: 10.4110/in.2020.20.e25. eCollection 2020 Jun.