Eating the enemy in Crohn's disease: An old theory revisited |
| |
| Authors: | Renzo Caprilli Pierre Lapaquette Arlette Darfeuille-Michaud |
| |
| Affiliation: | 1. University of Rome “La Sapienza”, Rome, Italy;2. Clermont Université, Université d''Auvergne, JE2526, F-63000, France;3. INRA, USC-2018, Clermont-Ferrand, France;4. Institut Universitaire de Technologie, Université d''Auvergne, F-63172 Aubière, France;1. Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts;3. Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts;5. Pathology Department, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts;6. Mucosal Immunology Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts;8. Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts;2. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts;7. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts;4. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri;1. Department of Biological Sciences, Indian Institute of Science Education and Research Bhopal-462023, India;2. University of Waterloo, Waterloo Institute for Nanotechnology, Waterloo, ON, Canada;1. Department of Pathology, University of Chicago, Chicago, IL 60637, USA;2. Department of Microbiology, University of Chicago, Chicago, IL 60637, USA;3. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA;4. Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA;5. Department of Genetics, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan;6. Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan;1. Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria, Australia;2. Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia;1. Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA;1. Division of Endocrinology Diabetes and Metabolism, University of Utah School of Medicine, Salt Lake City, UT 84112, USA;2. Department of Nutrition and Integrative Physiology, University of Utah College of Health and Program in Molecular Medicine, Salt Lake City, UT 84112, USA;3. Progenitor Life Sciences, Salt Lake City, UT 84108, USA |
| |
| Abstract: | Several old and new observations suggest the existence in Crohn's disease of a phagocytic disorder of macrophages related to impaired bactericidal activity of host cells or to the presence of invasive bacteria that have developed strategies to counteract macrophage killing. It was recently reported that disordered macrophage cytokine secretion underlies impaired acute inflammation and bacterial clearance in Crohn's disease. Secretion of proinflammatory cytokines by CD macrophages was impaired in response to E. coli or specific Toll-like receptor agonists. In addition, major advances in the etiology of Crohn's disease came from the existence of polymorphism in NOD2 and autophagy-related susceptibility genes (ATG16L1 and IRGM) in patients and from the identification of the presence of adherent-invasive E. coli (AIEC) colonizing the CD ileal mucosa and able to resist to macrophage killing. The role of impaired autophagy in Crohn's disease patients has been recently reinforced by the observation that the peptidoglycan receptor NOD2, in addition to sense intracellular bacteria, can induce autophagy by recruiting the critical autophagy protein ATG16L1 to the plasma membrane during bacterial internalization. Defects in autophagy might be the key element of the pathogenic pathway that lead to defective microbial killing, increased exposure to commensal and pathogenic intestinal bacteria and T cell activation. Defects in Paneth cells secreting lysozyme and antimicrobial peptides are observed in patients with ATG16L1 risk allele. Thus, the induction of autophagy or administration of preparations that mirrors the secretion of Paneth cells or both may be regarded as new therapeutic avenues for the treatment of Crohn's disease. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
