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'Nodophagy': New crossroads in Crohn disease pathogenesis.

ABSTRACT: Autophagy is a homeostatic pathway that processes and recycles damaged organelles and other cytoplasmic contents. While studies have implicated autophagy in the immune response to infection, the understanding of how the autophagic machinery specifically targets intracellular pathogens has remained elusive. Two recent studies have uncovered an autophagy-mediated immune response to bacteria through their detection by Nod receptors. In particular, Nod1 and Nod2 recruit the autophagic protein ATG16L1 to the plasma membrane at the bacterial entry site to promote an autophagy-dependent elimination of bacteria. In addition, Nod2 and ATG16L1 synergize to initiate an adaptive immune response to bacterial invasion by enhancing major histocompatibility complex (MHC) class II antigen presentation. These findings link two Crohn disease-associated susceptibility genes and reveal that cells expressing the risk-associated variants of ATG16L1 are defective in autophagy-mediated bacterial handling and antigen presentation. This could lead to bacterial persistence and contribute to the pathogenesis of the disease.

SUBMITTER: Ramjeet M

PROVIDER: S-EPMC3023615 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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'Nodophagy': New crossroads in Crohn disease pathogenesis.

Ramjeet Mahendrasingh M Hussey Séamus S Philpott Dana J DJ Travassos Leonardo H LH

Gut microbes 20100808 5

Autophagy is a homeostatic pathway that processes and recycles damaged organelles and other cytoplasmic contents. While studies have implicated autophagy in the immune response to infection, the understanding of how the autophagic machinery specifically targets intracellular pathogens has remained elusive. Two recent studies have uncovered an autophagy-mediated immune response to bacteria through their detection by Nod receptors. In particular, Nod1 and Nod2 recruit the autophagic protein ATG16L ...[more]

PMID: 21327039

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Project description:To formulate therapy goals, we aimed to define the relationship between fecal calprotectin and health-related quality of life in inflammatory bowel diseases (IBDs). This retrospective single-center cross-sectional study included ambulatory IBD patients who had completed standardized questionnaires comprising items of health-related quality of life (Short Inflammatory Bowel Disease Questionnaire) and clinical disease activity scores, and who had provided stool samples for calprotectin determination within 30 days of questionnaire completion. Correlation analyses were performed between the indicated parameters. Post hoc analysis was conducted, taking into account only data from patients with fecal calprotectin concentrations measured within 3 days of questionnaire completion. One hundred ninety-seven patients with Crohn disease and 111 patients with ulcerative colitis were enrolled in the study. Lower fecal calprotectin concentrations were associated with better health-related quality of life. The correlations were weak, but stronger if only fecal calprotectin concentrations measured within 3 days of questionnaire completion were included (results for 3 days; Crohn disease: n?=?86, rS?=?-0.419, P?<?0.001; ulcerative colitis: n?=?43, rS?=?-0.432, P?=?0.004). In Crohn disease, a significant correlation between fecal calprotectin concentration and health-related quality of life was found in patients with colonic involvement (n?=?59, rS?=?-0.470, P?<?0.001), but not in patients with purely ileal disease (n?=?27, rS?=?-0.268, P?=?0.18). Correlations between fecal calprotectin concentrations and clinical disease activity were also only weak to moderate. Owing to its moderate correlation with fecal calprotectin concentrations in IBD patients with colonic involvement, health-related quality of life should be used in combination with other markers for IBD management. This is even more important in isolated ileal Crohn disease, where no significant correlation between fecal calprotectin concentration and health-related quality of life was found. Especially for use in research studies, care should be taken to keep the time between clinical evaluation of IBD patients and the determination of fecal calprotectin concentrations as short as possible.

Dataset Information

'Nodophagy': New crossroads in Crohn disease pathogenesis.

Publications

'Nodophagy': New crossroads in Crohn disease pathogenesis.

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