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Updated: Jul 17, 2026
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Published on: July 3, 2026
Adherent-invasive Escherichia coli isolated from Crohn's disease patients induce granulomas in vitro
Sonia Meconi1, Alain Vercellone, Florence Levillain
1Department Molecular Mechanisms of Mycobacterial Infections, IPBS, CNRS UMR5089, Toulouse 31077, France.
Abstract:
Adherent-invasive Escherichia coli (AIEC) have been shown to be highly associated with ileal Crohn's disease (CD). AIEC survive within infected macrophages, residing within the phagolysosomal compartment where they take advantage of the low pH to replicate extensively. We investigated whether, like the tuberculous bacillus which also persists within macrophages, AIEC LF82 induces the formation of granulomas, which are a common histopathological feature of CD. For this purpose, we have taken advantage of an in vitro model of human granulomas that we recently developed, based on blood-derived mononuclear cells. We demonstrated that AIEC LF82 induces aggregation of infected macrophages, fusion of some of them to form multinucleated giant cells and subsequent recruitment of lymphocytes. Light microscopy and scanning electron microscopy analysis of the cell aggregates confirmed their granuloma features. This was further confirmed by histological analysis of granuloma sections. Noteworthy, this phenomenon can be reproduced by soluble protein extracts of AIEC LF82 coated onto beads. Although the cell aggregates not completely mimic natural CD-associated granulomas, they are very similar to early stages of epithelioid granulomas.
Insights
Adherent-invasive Escherichia coli (AIEC) can induce granuloma formation in vitro, mimicking early stages of Crohn's disease (CD) pathology. This finding sheds light on AIEC
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Adherent-invasive Escherichia coli (AIEC) are strongly linked to ileal Crohn's disease (CD).
- AIEC survive and replicate within macrophages by exploiting the low pH of the phagolysosome.
- Granulomas are a hallmark histopathological feature of Crohn's disease.
Purpose of the Study:
- To investigate if AIEC LF82 induces granuloma formation in an in vitro model.
- To compare AIEC-induced granulomas to those seen in Crohn's disease.
Main Methods:
- Utilized an in vitro model of human granulomas using blood-derived mononuclear cells.
- Infected macrophages with AIEC LF82 and observed cellular responses.
- Employed light microscopy, scanning electron microscopy, and histological analysis.
- Tested the effect of soluble protein extracts from AIEC LF82.
Main Results:
- AIEC LF82 induced macrophage aggregation and fusion into multinucleated giant cells.
- Lymphocytes were recruited to the developing cell aggregates.
- Microscopic and histological analyses confirmed granuloma-like features.
- Soluble protein extracts of AIEC LF82 could also induce these structures.
Conclusions:
- AIEC LF82 can induce the formation of structures resembling early-stage epithelioid granulomas in vitro.
- This model provides insights into the pathogenesis of Crohn's disease associated with AIEC.
- Further research is needed to fully elucidate the mechanisms and relevance to in vivo CD granulomas.
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