Role of autophagy defects and significance of adherent-invasive <i>Escherichia coli</i> in Crohn's disease development

Abstract

The aim of review. To present new data on a role of molecular genetic disorders of innate immunity at Crohn's disease (CD), and to demonstrate the role of adherent-invasive Escherichia coli (AIEC) as the microorganisms potentially involved in CD development.Summary. According to modern concept, etiology of CD has complex nature and is determined by genetic predisposition, infectious agents and environmental factors. Alteration of autophagy process (defects of NOD2/ CARD15, ATG16L1, IRGM genes) is one of genetically determined disorders of innate immunity typical for CD. Besides that intestinal dysbiotic disorders associated with elevation of quantity of microorganisms, possessing pathogenic potential, in particular AIEC is characteristic for CD. This phenotype of microorganisms has capacity of adhesion to mucosal epithelial cells, invasion, and active replication inside macrophages. In patients with genetic predisposition AIEC replication in macrophages at reduced clearance of microorganisms due to alteration of autophagy process can induce the unsound immune response with development inflammatory changes characteristic for CD.Conclusion. Intestinal dysbiosis associated with elevation of quantity of microorganisms, possessing pathogenic potential (AIEC), as well as genetically — determined defects of innate immunity (autophagy alteration) lay in a basis of up-to-date model of CD development. Undoubtedly, such model is most likely relevant only for selected part of CD patients, nevertheless for the present moment it is the basic for the further studying of CD etiopathogenesis.

Keywords

• crohn's disease
• innate immunity
• autophagy
• xenophagy
• microbiota
• nod2/card15
• atg16l1
• irgm
• escherichia coli
• aiec