Skip to Main content Skip to Navigation
Journal articles

The regenerating family member 3 β instigates IL-17A-mediated neutrophil recruitment downstream of NOD1/2 signalling for controlling colonisation resistance independently of microbiota community structure

Nadine Waldschmitt 1 Sho Kitamoto 2 Thomas Secher 3 Vassiliki Zacharioudaki 1 Olivier Boulard 1 Emilie Floquet 1 Myriam Delacre 1 Bruno Lamas 4, 5 Hang-Phuong Pham 6, 7 Adrien Six 8 Mathias Richard 4 Jean-Charles Dagorn 9 Gérard Eberl 10 Philippe Langella 4 Jean-Marc Chatel 4 Bernhard Ryffel 3 Juan Lucio Iovanna 9 Lionel Poulin 1 Harry Sokol 4, 11, 5 Nobuhiko Kamada 2 Mathias Chamaillard 1
1 CIIL - Centre d’Infection et d’Immunité de Lille (CIIL) - INSERM U1019 - UMR 9017
2 Division of Gastroenterology, Department of Internal Medicine [Ann Arbor]
3 INEM - Immunologie et Neurogénétique Expérimentales et Moléculaires
4 MICALIS - MICrobiologie de l'ALImentation au Service de la Santé
5 LBM UMR 7203 - Laboratoire des biomolécules
6 CHU Pitié-Salpêtrière [AP-HP]
7 ILTOO Pharma
8 I3 - Immunologie - Immunopathologie - Immunothérapie
9 CRCM - Centre de Recherche en Cancérologie de Marseille
10 Microenvironnement et Immunité
11 Department of Gastroenterology, Saint Antoine Hospital, Assistance Publique – Hopitaux de Paris
Abstract : Loss of the Crohn’s disease predisposing NOD2 gene results in an intestinal microenvironment conducive for colonisation by attaching-and-effacing enteropathogens. However, it remains elusive whether it relies on the intracellular recruitment of the serine-threonine kinase RIPK2 by NOD2, a step that is required for its activation of the transcription factor NF-κB. Colonisation resistance was evaluated in wild type and mutant mice, as well as in ex-germ-free (ex-GF) mice which were colonised either with faeces from Ripk2-deficient mice or with bacteria with similar preferences for carbohydrates to those acquired by the pathogen. The severity of the mucosal pathology was quantified at several time points postinfection by using a previously established scoring. The community resilience in response to infection was evaluated by 16S ribosomal RNA gene sequence analysis. The control of pathogen virulence was evaluated by monitoring the secretion of Citrobacter-specific antibody response in the faeces. Primary infection was similarly outcompeted in ex-GF Ripk2-deficient and control mice, demonstrating that the susceptibility to infection resulting from RIPK2 deficiency cannot be solely attributed to specific microbiota community structures. In contrast, delayed clearance of Citrobacter rodentium and exacerbated histopathology were preceded by a weakened propensity of intestinal macrophages to afford innate lymphoid cell activation. This tissue protection unexpectedly required the regenerating family member 3β by instigating interleukin (IL) 17A-mediated neutrophil recruitment to the intestine and subsequent phosphorylation of signal transducer and activator of transcription 3. These results unveil a previously unrecognised mechanism that efficiently protects from colonisation by diarrhoeagenic bacteria early in infection.
Keywords : antibacterial peptide barrier function interleukins macrophages
Document type :
Journal articles
Complete list of metadatas
https://hal-cnrs.archives-ouvertes.fr/hal-02126570
Contributor : Valérie Quesniaux <>
Submitted on : Saturday, May 11, 2019 - 9:42:09 PM
Last modification on : Saturday, September 26, 2020 - 11:44:12 PM

Identifiers

Collections

CNRS | INRA | RIIP | RIIP_LILLE | AGROPARISTECH | UNIV-ORLEANS | UNIV-LILLE | UNIV-PARIS-SACLAY | PASTEUR | I3 | ENSCP | INC-CNRS | ENS-PARIS | UNIV-AMU | SORBONNE-UNIVERSITE | CRCM | PARISTECH | LBM | SU-MEDECINE | SU-SCIENCES | INRAE | CIIL | ESPCI-PSL | PSL | ESPCI

Citation

Nadine Waldschmitt, Sho Kitamoto, Thomas Secher, Vassiliki Zacharioudaki, Olivier Boulard, et al.. The regenerating family member 3 β instigates IL-17A-mediated neutrophil recruitment downstream of NOD1/2 signalling for controlling colonisation resistance independently of microbiota community structure. Gut, BMJ Publishing Group, In press, in oress, pp.gutjnl-2018-316757. ⟨10.1136/gutjnl-2018-316757⟩. ⟨hal-02126570⟩

Export

BibTeX TEI DC DCterms EndNote

Share

Metrics

Record views

429