Evidence map›Paper›PMID 23973919›Full record

ArticleGastroenterology2013

Atg16l1 is required for autophagy in intestinal epithelial cells and protection of mice from Salmonella infection.

Kara L Conway, Petric Kuballa, Joo-Hye Song, Khushbu K Patel, Adam B Castoreno, Omer H Yilmaz, Humberto B Jijon, Mei Zhang, Leslie N Aldrich, Eduardo J Villablanca and 13 more

Abstract read
In one paragraph

Article in Gastroenterology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers.

0numbers the graph read from it
0cells of the map it votes in
153citing papers in PubMed
16.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

153 citing papers in PubMed, 230 citations in OpenAlex.

  1. Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026
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93 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors at 5 institutions in 1 country.

Kara L ConwayGastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts; Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Petric Kuballa
Joo-Hye Song
Khushbu K Patel
Adam B Castoreno
Omer H Yilmaz
Humberto B Jijon
Mei Zhang
Leslie N Aldrich
Eduardo J Villablanca
Joanna M Peloquin
Gautam Goel
In-Ah Lee
Emiko Mizoguchi
Hai Ning Shi
Atul K Bhan
Stanley Y Shaw
Stuart L Schreiber
Herbert W Virgin
Alykhan F Shamji
Thaddeus S Stappenbeck
Hans-Christian Reinecker
Ramnik J Xavier
Harvard University · USMassachusetts General Hospital · USBroad Institute · USMassachusetts Institute of Technology · USWashington University in St. Louis · US

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3M
ROLE OF DIETARY CONSTITUENTS ON GENE EXPRESSION IN INTESTINAL EPITHELIUMP30DK040561 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI CHRISTOPHER P DUGGAN · 1994 to 2026
$31.6M
Xenograft and Isograft CoreP01DK033506 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI WALKER, W ALLAN · 1986 to 2015
$24.2M
Antigen Recognition at Intestinal Epithelial InterphasesR01DK068181 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI REINECKER, HANS-CHRISTIAN · 2005 to 2017
$5.2M
ATG16L1 T300A: genetics to biologyR01DK097485 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI XAVIER, RAMNIK J · 2013 to 2021
$4.1M
IMMUNITY AND PATHOGENESIS OF A NOVEL NOROVIRUSR01AI054483 · NIAID · WASHINGTON UNIVERSITY · PI VIRGIN, HERBERT W · 2003 to 2012
$3.7M
Toll-like Receptors and the Intestinal EpitheliumR01DK060049 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI XAVIER, RAMNIK J · 2002 to 2011
$3.5M
Autophagy genes and the microbiome in Crohn's DiseaseR01DK092405 · NIDDK · BROAD INSTITUTE, INC. · PI XAVIER, RAMNIK J · 2012 to 2014
$2.0M
SUSCEPTIBILILTY GENE-VIRUS INTERACTIONS IN INFLAMMATORY BOWEL DISEASER01AI084887 · NIAID · WASHINGTON UNIVERSITY · PI STAPPENBECK, THADDEUS S, VIRGIN, HERBERT W · 2010 to 2014
$1.9M
Immunomodulatory effects of intestinal helminthes on mucosal immunityR01DK082427 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI SHI, HAI NING · 2010 to 2014
$1.9M
Regulation of the Intestinal Stem Cell Niche in AgingR00AG045144 · NIA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI YILMAZ, OMER · 2014 to 2016
$740k
Mechanisms of Innate Immune Regulation for Mucosal HomeostasisR56AI093588 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI REINECKER, HANS-CHRISTIAN · 2011 to 2011
$362k
NIAID NIH HHS AI054483NIAID NIH HHS AI093588NIAID NIH HHS R01 AI054483NIAID NIH HHS R01 AI084887NIAID NIH HHS R56 AI093588NIA NIH HHS K99 AG045144NIA NIH HHS R00 AG045144NIDDK NIH HHS DK033506NIDDK NIH HHS DK043351NIDDK NIH HHS DK060049NIDDK NIH HHS DK068181NIDDK NIH HHS DK082427NIDDK NIH HHS DK092405NIDDK NIH HHS DK097485NIDDK NIH HHS P01 DK033506NIDDK NIH HHS P30 DK040561NIDDK NIH HHS P30 DK043351NIDDK NIH HHS R01 DK060049NIDDK NIH HHS R01 DK068181NIDDK NIH HHS R01 DK082427NIDDK NIH HHS R01 DK092405NIDDK NIH HHS R01 DK097485
6 · The paper itself

Abstract

BACKGROUND &

aimsIntestinal epithelial cells aid in mucosal defense by providing a physical barrier against entry of pathogenic bacteria and secreting antimicrobial peptides (AMPs). Autophagy is an important component of immune homeostasis. However, little is known about its role in specific cell types during bacterial infection in vivo. We investigated the role of autophagy in the response of intestinal epithelial and antigen-presenting cells to Salmonella infection in mice.

methodsWe generated mice deficient in Atg16l1 in epithelial cells (Atg16l1(f/f) × Villin-cre) or CD11c(+) cells (Atg16l1(f/f) × CD11c-cre); these mice were used to assess cell type-specific antibacterial autophagy. All responses were compared with Atg16l1(f/f) mice (controls). Mice were infected with Salmonella enterica serovar typhimurium; cecum and small-intestine tissues were collected for immunofluorescence, histology, and quantitative reverse-transcription polymerase chain reaction analyses of cytokines and AMPs. Modulators of autophagy were screened to evaluate their effects on antibacterial responses in human epithelial cells.

resultsAutophagy was induced in small intestine and cecum after infection with S typhimurium, and required Atg16l1. S typhimurium colocalized with microtubule-associated protein 1 light chain 3β (Map1lc3b or LC3) in the intestinal epithelium of control mice but not in Atg16l1(f/f) × Villin-cre mice. Atg16l1(f/f) × Villin-cre mice also had fewer Paneth cells and abnormal granule morphology, leading to reduced expression of AMPs. Consistent with these defective immune responses, Atg16l1(f/f) × Villin-cre mice had increased inflammation and systemic translocation of bacteria compared with control mice. In contrast, we observed few differences between Atg16l1(f/f) × CD11c-cre and control mice. Trifluoperazine promoted autophagy and bacterial clearance in HeLa cells; these effects were reduced upon knockdown of ATG16L1.

conclusionsAtg16l1 regulates autophagy in intestinal epithelial cells and is required for bacterial clearance. It also is required to prevent systemic infection of mice with enteric bacteria.

Indexed as

AnimalsAutophagyAutophagy-Related ProteinsCarrier ProteinsCD11c AntigenDisease Models, AnimalHeLa CellsHumansIntestinal MucosaMiceMice, KnockoutMicrofilament ProteinsMicrotubule-Associated ProteinsSalmonella Infections, AnimalSalmonella typhimuriumAtg16l1 protein, mouseAutophagy-Related ProteinsCarrier ProteinsCD11c AntigenMap1lc3b protein, mouseMicrofilament ProteinsMicrotubule-Associated ProteinsvillinAMPantimicrobial peptideATGAutophagyautophagy-related geneDiscosoma sp. red fluorescent proteindsRedEGFPenhanced green fluorescent proteinFAEfollicle-associated epitheliumGFPgreen fluorescent proteinILinterleukinIntestinal BarrierLC3light chain 3Map1lc3bMEFmesenteric lymph nodesmessenger RNAmicrotubule-associated protein 1 light chain 3bMLNmouse embryonic fibroblastMouse ModelmRNAMucosaSalmonella-containing vacuoleSCVTFPtrifluoperazine

Identifiers

PMID23973919
PMCPMC3840157
OpenAlexW1975510193

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.