The Crohn's disease: associated ATG16L1 variant and<i>Salmonella</i>invasion

Messer, Jeannette S.; Murphy, SB; Logsdon, Mark F; Lodolce, James P.; Grimm, Wesley A; Bartulis, Sarah; Vogel, Tiphanie P.; Burn, Melisa; Boone, David L.

doi:10.1136/bmjopen-2013-002790

Cited by 28 publications

(38 citation statements)

References 32 publications

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“…Cells from patients homozygous for the T300A variant, or epithelial cells transduced with this variant, fail to clear intracellular microbes indicating that reduced pathogen clearance in patients with this variant might contribute to risk of CD (Kuballa et al, 2008). Atg16l1 facilitates bacterial invasion and the ATG16L1 T300A variant reduces invasion of human cells by Salmonella (Jeannette et al, 2013). Mice lacking Atg16l1 in haematopoietic cells showed several features of dysfunctional immune homeostasis, including impaired Paneth cell function and hypersecretion of IL-1β and IL-18 from macrophages following stimulation with lipopolysaccharide (LPS) (Saitoh et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

The protection role of Atg16l1 in CD11c + dendritic cells in murine colitis

et al. 2017

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The autophagy-related 16-like 1 gene (Atg16l1) is associated with inflammatory bowel disease (IBD) and has been shown to play an essential role in paneth cell function and intestinal homeostasis. However, the functional consequences of Atg16l1 deficiency in myeloid cells, particularly in dendritic cells (DCs), are not fully characterized. The aim of this study is to investigate the functional consequence of Atg16l1 in CD11c+ DCs in murine colitis. We generated mice deficient in Atg16l1 in CD11c+ DCs. Dextran Sulfate Sodium (DSS) and S. typhimurium infection induced colitis was used to assess the role of DCs specific Atg16l1 deficiency in vivo in murine colitis. Bone marrow derived dendritic cells (BMDC) were isolated and autophagy function was assessed with microtubule-associated protein 1 light chain 3β (Map1lc3b or LC3) by western blot. Uptake of Salmonella enteric serovar typhimurium (S. typhimurium) was assessed by flow cytometry and transmission electron microscopy (TEM). The production of reactive oxygen species (ROS) and intracellular S. typhimurium killing in BMDCs were assessed. We showed worsened colonic inflammation in Atg16l1 deficiency mice in DSS induced murine colitis with increased proinflammatory cytokines of IL-1β and TNF-α. Mechanistic studies performed in primary murine BMDCs showed that Atg16l1 deficiency increased ROS production, reduced microbial killing and impaired antigen processing for altered intracellular trafficking. Together, these results indicate impaired CD11c+ DCs function with Atg16l1 deficiency contributes to the severity of murine colitis.

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Section: Introductionmentioning

confidence: 99%

The protection role of Atg16l1 in CD11c + dendritic cells in murine colitis

et al. 2017

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“…This mask extracts bright or dark regions of an object, and can be further refined with Peak and/or Range masks. Peak mask [16] can be used to separate connected spots in a Spot mask, while to select spots within a certain range of pixel values, Range mask is an option. Sometimes, when the fluorescence background of an image is high and appears spotty (especially when the Extended Depth of Field – EDF function is activated during file acquisition), it may result in many more spots masked, causing erroneously high spot counts.…”

Section: Troubleshooting Masksmentioning

confidence: 99%

Masks in imaging flow cytometry

Dominical

Samsel

McCoy

2017

Methods

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Data analysis in imaging flow cytometry incorporates elements of flow cytometry together with other aspects of morphological analysis of images. A crucial early step in this analysis is the creation of a mask to distinguish the portion of the image upon which further examination of specified features can be performed. Default masks are provided by the manufacturer of the imaging flow cytometer but additional custom masks can be created by the individual user for specific applications. Flawed or inaccurate masks can have a substantial negative impact on the overall analysis of a sample, thus great care must be taken to ensure the accuracy of masks. Here we discuss various types of masks and cite examples of their use. Furthermore we provide our insight for how to approach selecting and assessing the optimal mask for a specific analysis.

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“…Other models also need to be considered since autophagy can benefit viruses and bacteria including Salmonella by providing membranes or other factors that support replication (65-69). Additionally, autophagy genes have potent immuno-suppressive functions.…”

Section: Autophagy and Intestinal Immunitymentioning

confidence: 99%

Autophagy, viruses, and intestinal immunity

Kernbauer¹,

Cadwell²

2014

Current Opinion in Gastroenterology

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Purpose of review To highlight recent findings that identify an essential role for the cellular degradative pathway of autophagy in governing a balanced response to intestinal pathogens and commensals. Recent findings Following the genetic association of autophagy with inflammatory bowel disease (IBD) susceptibility, increasing evidence indicate that this pathway functions in various epithelial lineages to support the intestinal barrier. New studies are also revealing that autophagy proteins dictate the quality and magnitude of immune responses. Mouse models in particular suggest that autophagy and IBD susceptibility genes regulate inflammatory responses to viruses, a finding that coincides with an increasing appreciation that viruses have intricate interactions with the host and the microbiota beyond the obvious host-pathogen relationship. Summary Autophagy and other immunological or stress response pathways intersect in mucosal immunity to dictate the response to pathogenic and commensal agents. The development of novel treatment strategies as well as prognostic and diagnostic tools for gastrointestinal disorders will be greatly facilitated by a deeper understanding of these interactions at the cell type and microbe-specific manner, which includes less appreciated components of the microbiota such as eukaryotic and prokaryotic viruses.

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The Crohn's disease: associated ATG16L1 variant andSalmonellainvasion

Cited by 28 publications

References 32 publications

The protection role of Atg16l1 in CD11c + dendritic cells in murine colitis

The protection role of Atg16l1 in CD11c + dendritic cells in murine colitis

Masks in imaging flow cytometry

Autophagy, viruses, and intestinal immunity

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