A new avenue to investigate: the autophagic process. From Crohn's disease to Chlamydia.
The finding that a variant (T300A) of the autophagyrelated 16-like 1 (ATG16L1) gene is associated with Crohn's disease suggests that the inability to eliminate intestinal intracellular microbes via (macro)autophagy may be involved in the pathogenesis of this disease. The variant induces an autophagy-associated defect in Paneth cells, specialized cells in the crypts of Lieberkuhn within the small intestine that secrete defensins and other antimicrobial peptides. Moreover, other loci, IRGM and LRRK2 involved in autophagy and implicated in clearance of intracellular bacteria have been found to be associated with Crohn's disease. These unexpected findings have changed the focus of research in Crohn's disease and have stimulated an in-depth study of the complex process of autophagy. Autophagy is regulated by many genes and is emerging as a central player in the immunologic control of intracellular bacteria. Chlamydia trachomatis is able to inhibit apoptosis and the production of nuclear factor kappa B (NFkappaB) in order to survive in the host. Extensive studies on association of genes regulating the inflammatory response in experimental models and in humans as revised in other sections of this supplement have failed to explain the longterm complications of C. trachomatis infection. The advances in the molecular pathways of Chlamydia infection and their effects on the Golgi apparatus and other cytoplasmic organelles suggests that defects in autophagic genes may predispose the host to chronic infection and be responsible for the long-term complications. A new genomic approach of the complete autophagic pathway may reveal new insight to understand the presence of a complication in affected individuals, even if at present there is no evidence that C. trachomatis is affected by this pathway.
Peña
A S
AS
Laboratory of Immunogenetics, Department of Pathology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands. pena.as@gmail.com
Karimi
O
O
Crusius
J B A
JB
D000818:Animals; D001343:Autophagy; D002690:Chlamydia Infections / Q000209:etiology* / Q000276:immunology; D002692:Chlamydia trachomatis; D003424:Crohn Disease / Q000209:etiology* / Q000276:immunology; D006801:Humans; D057131:Immune Evasion; D007371:Interferon-gamma / Q000502:physiology
D007371:Interferon-gamma