title: Defective innate immunity in inflammatory bowel disease: a Crohn's disease exclusivity?
abstract: OBJECTIVE
  This review summarizes the recent developments in support of the immunodeficiency model of Crohn's disease.
  
  
  RESULTS
  The demonstration of impaired acute inflammation in Crohn's disease provides a novel mechanism for its pathogenesis, with diminished macrophage cytokine production and neutrophil recruitment leading to reduced bacterial clearance. The innate immune response may be further overwhelmed by other factors. The mucosal barrier in Crohn's patients is disrupted, with abnormal ultrastructure as well as antibacterial defensin deficiency. Specific bacterial agents may contribute and one promising candidate, adherent-invasive Escherichia coli, has recently been described. An interaction between Nod2 and the autophagy system has been elucidated, with direct consequences for bacterial clearance, and the most recent genome-wide association study meta-analysis has extended the number of Crohn's disease susceptibility loci to 71. The spectrum of congenital immunodeficiency disorders recognized to develop Crohn's-like inflammatory bowel disease is also expanding. Conversely, no specific immunodeficiency has so far been observed in ulcerative colitis, in which the defect appears to be failure of inflammation termination and resolution.
  
  
  CONCLUSIONS
  Recent advances continue to highlight defects in innate immunity in Crohn's patients. Similar abnormalities may extend to other granulomatous disorders, but not diseases such as ulcerative colitis.
authors.affiliation: Centre for Molecular Medicine, University College London, London, UK. d.marks@ucl.ac.uk
authors.forename: Daniel J B
authors.initials: DJ
authors.lastname: Marks
mesh_terms: D003424:Crohn Disease / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D055106:Genome-Wide Association Study; D006801:Humans; D007113:Immunity, Innate; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000382:microbiology; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology