Journal ArticleDOI
Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry
Leonardo H. Travassos,Leticia A.M. Carneiro,Mahendrasingh Ramjeet,Seamus Hussey,Seamus Hussey,Yun Gi Kim,Joao G. Magalhaes,Linda Yuan,Fraser Soares,Evelyn Chea,Lionel Le Bourhis,Ivo G Boneca,Abdelmounaaim Allaoui,Nicola L. Jones,Gabriel Núñez,Stephen E. Girardin,Dana J. Philpott +16 more
TLDR
The results link bacterial sensing by Nod proteins to the induction of autophagy and provide a functional link between Nod2 and ATG16L1, which are encoded by two of the most important genes associated with Crohn's disease.Abstract:
Autophagy is emerging as a crucial defense mechanism against bacteria, but the host intracellular sensors responsible for inducing autophagy in response to bacterial infection remain unknown. Here we demonstrated that the intracellular sensors Nod1 and Nod2 are critical for the autophagic response to invasive bacteria. By a mechanism independent of the adaptor RIP2 and transcription factor NF-kappaB, Nod1 and Nod2 recruited the autophagy protein ATG16L1 to the plasma membrane at the bacterial entry site. In cells homozygous for the Crohn's disease-associated NOD2 frameshift mutation, mutant Nod2 failed to recruit ATG16L1 to the plasma membrane and wrapping of invading bacteria by autophagosomes was impaired. Our results link bacterial sensing by Nod proteins to the induction of autophagy and provide a functional link between Nod2 and ATG16L1, which are encoded by two of the most important genes associated with Crohn's disease.read more
Citations
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Microbial Disruption of Autophagy Alters Expression of the RISC Component AGO2, a Critical Regulator of the miRNA Silencing Pathway
Michal Sibony,Michal Sibony,Majd Abdullah,Laura Greenfield,Deepa Raju,Ted Wu,David M. Rodrigues,Esther Galindo-Mata,Heidi Mascarenhas,Dana J. Philpott,Mark S. Silverberg,Mark S. Silverberg,Nicola L. Jones +12 more
TL;DR: Autophagy is involved in the regulation of the critical miRISC component AGO2 in epithelial and immune cells and primary intestinal epithelial cells, suggesting a novel mechanism by which enteric microbes could influence miRNA to promote disease.
Journal ArticleDOI
Frontline Science: Autophagy is a cell autonomous effector mechanism mediated by NLRP3 to control Trypanosoma cruzi infection
TL;DR: Results indicate autophagy as an effector mechanism mediated by NLRP3 to control T. cruzi infection and indicate cell‐autonomous and cross‐regulated processes involved in host resistance against infections.
Journal ArticleDOI
Innate Immune Sensors and Gastrointestinal Bacterial Infections
TL;DR: The nature and impact of pathogen:receptor interactions, their impact upon pathogenesis, and the relevance of pattern recognition receptors in the development of therapies for gastrointestinal diseases are addressed.
Journal ArticleDOI
Translating Treg Therapy for Inflammatory Bowel Disease in Humanized Mice.
Sushmita Negi,Sheetal Saini,Nikunj Tandel,Kiran Chandra Sahu,Ravi Prakash Mishra,Rajeev K Tyagi +5 more
TL;DR: In this article, the authors review the mechanisms of action and functional importance of Tregs during the pathogenesis of inflammatory bowel disease and modulating the disease induced inflammation as well as role of mouse models including humanized mice repopulated with the human immune system (HIS) to study the IBD.
Journal ArticleDOI
Regulation of antiapoptotic and cytoprotective pathways in colonic epithelial cells in ulcerative colitis
TL;DR: It is shown that epithelial cells in ulcerative colitis responds to the hostile microenvironment by activation of cytoprotective pathways that tend to counteract the cytotoxic effects of inflammation, however, the present studies also show that epithelium cells produce increased amounts of reactive oxygen species during stimulation with tumor necrosis factor-α and interferon-γ resulting in DNA instability.
References
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Autophagy fights disease through cellular self-digestion
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Journal ArticleDOI
Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease
Jean-Pierre Hugot,Mathias Chamaillard,Mathias Chamaillard,Habib Zouali,Suzanne Lesage,Jean-Pierre Cézard,Jacques Belaiche,Sven Almer,Curt Tysk,Colm O'Morain,Miquel A. Gassull,Vibeke Binder,Yigael Finkel,Antoine Cortot,Robert Modigliani,Pierre Laurent-Puig,C. Gower-Rousseau,J. Macry,Jean-Frederic Colombel,Mourad Sahbatou,Gilles Thomas,Gilles Thomas +21 more
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Journal ArticleDOI
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Journal ArticleDOI
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Stephen E. Girardin,Ivo G. Boneca,Jérôme Viala,Mathias Chamaillard,Agnès Labigne,Gilles Thomas,Dana J. Philpott,Philippe J. Sansonetti +7 more
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TL;DR: A set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes are presented.
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