Communication Dans Un Congrès Année : 2023

Interaction between Chitinase 3-like 1 (CHI3L1) and bacterial protein ChiA : a decisive step for Crohn’s disease-associated adherent and invasive E. coli to enter within human macrophages.

Résumé

Introduction: Crohn’s Disease (CD)-associated adherent-invasive E. coli (AIEC) are to survive and replicate within macrophages inducing inflammatory response. Besides, macrophages from CD patients are defective to control AIEC replication. It has been recently shown that anti-TNF agents limit AIEC replication within macrophages by modulating Chitinase 3-Like 1 (CHI3L1) expression. AIEC bacteria adhere to IECs through the interaction between the AIEC protein ChiA and CHI3L1. Whether CHI3L1-ChiA interaction could play a role in promoting AIEC entry into macrophages is unknown. Aims & Methods: The physical interaction between these two proteins have been assessed by Western blot and measured by MST technology. Human cultured macrophages (THP-1) and human macrophages-derived monocytes (hMDM) were infected with the reference AIEC LF82 strain (LF82 AIEC) and the corresponding chiA-negative mutant (LF82∆chiA). They were also infected by fluorescence bacteria in order to visualise them during coinfection observed by cell-live or confocal imagery. Other AIEC strains, isolated from CD patients with different chiA polymorphisms were also used. Anti-CHI3L1 antibodies have been used to block ChiA-CHI3L1 interaction. All these conditions were tested on mice C57Bl6 with colitis induced by DSS. Results: LF82∆chiA bacteria uptake (at 1h post-infection) within human macrophages was reduced of 40 % and 45 % in THP-1 and hMDM, respectively, compared to wild type LF82 (p < 0.05). Live imaging recording macrophages infection with a mixture (1:1 ratio) of LF82 AIEC WT (labelled in red) and the LF82∆chiA (labelled in green), showed that LF82∆chiA mutant had a two-fold reduced entry into hMDM (p < 0.05). LF82∆chiA colonises considerably less of the ileal and colonic mucosa of mice. A reduction of this deleted strain in the lamina propria, the intestinal macrophage niche, compared with the wild-type strain is expected. Blockage of ChiA-CHI3L1 interaction using anti-CHI3L1 antibodies significantly decreased the survival ability within macrophages of several AIEC bacteria strains isolated from CD patients including LF82 (p<0.05), demonstrating that this mechanism may be common to different AIEC strains. Conclusion: ChiA-CHI3L1 interaction plays a key role in the CD-associated AIEC ability to enter within macrophages. Blocking this interaction may be promising to target AIEC in patients with CD.

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hal-04974242 , version 1 (03-03-2025)

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  • HAL Id : hal-04974242 , version 1

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Margot Fargeas, Frédéric Faure, Clara Douadi, Anthony Buisson, Nicolas Barnich. Interaction between Chitinase 3-like 1 (CHI3L1) and bacterial protein ChiA : a decisive step for Crohn’s disease-associated adherent and invasive E. coli to enter within human macrophages.. Société Française de Microbiologie (SFM), Oct 2023, Rennes, France. ⟨hal-04974242⟩
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