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Chronic Salmonella Infection Induced Intestinal Fibrosis
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Trained immunity modulates inflammation-induced fibrosis.

Mohamed Jeljeli1,2, Luiza Gama Coelho Riccio1,3, Ludivine Doridot1

  • 1Institut Cochin, INSERM U1016, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

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|December 13, 2019
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Summary

Low-dose lipopolysaccharide (LPS) trained macrophages alleviate fibrosis and inflammation in systemic sclerosis (SSc) models, while BCG-trained macrophages worsen disease. This suggests trained immunity offers therapeutic potential for SSc and related fibrotic disorders.

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Area of Science:

  • Immunology
  • Cell Biology
  • Pathology

Background:

  • Chronic inflammation and fibrosis are often driven by dysregulated immune responses, particularly involving macrophages.
  • Macrophages possess the ability to develop memory-like properties following antigen exposure, a phenomenon known as trained immunity.

Purpose of the Study:

  • To investigate the impact of Bacillus Calmette-Guérin (BCG) or low-dose lipopolysaccharide (LPS) stimulation on macrophage phenotype, cytokine production, chromatin, and metabolic profiles.
  • To evaluate the therapeutic potential of trained macrophages in a mouse model of systemic sclerosis (SSc) and in vitro.

Main Methods:

  • Macrophages were stimulated with BCG or low-dose LPS.
  • Phenotypic, cytokine, chromatin, and metabolic changes in macrophages were analyzed.
  • The effects of trained macrophages were assessed in a mouse model of SSc and through co-culture with SSc fibroblasts.

Main Results:

  • Low-dose LPS training ameliorated fibrosis and inflammation in an SSc mouse model.
  • BCG training exacerbated disease severity in the SSc mouse model.
  • Adoptive transfer of LPS-trained macrophages showed beneficial effects, while BCG-trained macrophages had detrimental effects.
  • Co-culture with LPS-trained macrophages reduced the pro-fibrotic and inflammatory characteristics of SSc fibroblasts.

Conclusions:

  • Trained immunity, induced by low-dose LPS, demonstrates therapeutic promise for treating systemic sclerosis (SSc) and other autoimmune and inflammatory fibrotic conditions.
  • BCG-induced trained immunity had adverse effects in the SSc model, highlighting the need for specific training protocols.