Keqiang Chen1, Teizo Yoshimura2, Wanghua Gong3, Cuimeng Tian1,4, Jiaqiang Huang1,5, Giorgio Trinchieri6, Ji Ming Wang7. 1. Laboratory of Cancer ImmunoMetabolism, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA. 2. Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan. 3. Basic Research Program, Leidos Biomedical Research, Inc., Frederick, MD 21702, USA. 4. Beijing Tuberculosis and Thoracic Tumor Research Institute/Beijing Chest Hospital, Capital Medical University, Beijing 101149, China. 5. College of Life Sciences, Beijing Jiaotong University, Beijing 100044, China. 6. Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. 7. Laboratory of Cancer ImmunoMetabolism, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA wangji@mail.nih.gov.
Abstract
Host-derived antimicrobial peptides play an important role in the defense against extracellular bacterial infections. However, the capacity of antimicrobial peptides derived from macrophages as potential antibacterial effectors against intracellular pathogens remains unknown. In this study, we report that normal (wild-type, WT) mouse macrophages increased their expression of cathelin-related antimicrobial peptide (CRAMP, encoded by Camp) after infection by viable E. coli or stimulation with inactivated E. coli and its product lipopolysaccharide (LPS), a process involving activation of NF-κB followed by protease-dependent conversion of CRAMP from an inactive precursor to an active form. The active CRAMP was required by WT macrophages for elimination of phagocytosed E. coli, with participation of autophagy-related proteins ATG5, LC3-II and LAMP-1, as well as for aggregation of the bacteria with p62 (also known as SQSTM1). This process was impaired in CRAMP-/- macrophages, resulting in retention of intracellular bacteria and fragmentation of macrophages. These results indicate that CRAMP is a critical component in autophagy-mediated clearance of intracellular E. coli by mouse macrophages.
Host-derived antimicrobial peptides play an important role in the defense against extracellular bacterial infections. However, the capacity of antimicrobial peptides derived from macrophages as potential antibacterial effectors against intracellular pathogens remains unknown. In this study, we report that normal (wild-type, WT) pan class="Species">mouse macrophages increased their expression of cathelin-related antimicrobial peptide (CRAMP, encoded by Camp) after infection by viable E. coli or stimulation with inactivated E. coli and its product lipopolysaccharide (LPS), a process involving activation of NF-κB followed by protease-dependent conversion of CRAMP from an inactive precursor to an active form. The active CRAMP was required by WT macrophages for elimination of phagocytosed E. coli, with participation of autophagy-related proteins ATG5, LC3-II and LAMP-1, as well as for aggregation of the bacteria with p62 (also known as SQSTM1). This process was impaired in CRAMP-/- macrophages, resulting in retention of intracellular bacteria and fragmentation of macrophages. These results indicate that CRAMP is a critical component in autophagy-mediated clearance of intracellular E. coli by mouse macrophages.
Authors: Marisa Ponpuak; Alexander S Davis; Esteban A Roberts; Monica A Delgado; Christina Dinkins; Zijiang Zhao; Herbert W Virgin; George B Kyei; Terje Johansen; Isabelle Vergne; Vojo Deretic Journal: Immunity Date: 2010-03-04 Impact factor: 31.745
Authors: Jennifer Raisch; Emmanuel Buc; Mathilde Bonnet; Pierre Sauvanet; Emilie Vazeille; Amélie de Vallée; Pierre Déchelotte; Claude Darcha; Denis Pezet; Richard Bonnet; Marie-Agnès Bringer; Arlette Darfeuille-Michaud Journal: World J Gastroenterol Date: 2014-06-07 Impact factor: 5.742