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Inflammation Research
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28-09-2024 | Pyarthrosis | Original Research Paper

Trained immunity of synovial macrophages is associated with exacerbated joint inflammation and damage after Staphylococcus aureus infection

Authors: Peter Silva Rocha, Adryan Aparecido Silva, Celso Martins Queiroz-Junior, Amanda Dias Braga, Thaiane Pinto Moreira, Mauro Martins Teixeira, Flávio Almeida Amaral

Published in: Inflammation Research | Issue 11/2024

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Abstract

Objectives

Investigate whether and which synoviocytes would acquire trained immunity characteristics that could exacerbate joint inflammation following a secondary Staphylococcus aureus infection.

Methods

Lipopolysaccharide (LPS) and S. aureus were separately or double injected (21 days of interval) into the tibiofemoral joint cavity of male C57BL/6 mice. At different time points after these stimulations, mechanical nociception was analyzed followed by the analysis of signs of inflammation and damage in the affected joints. The trained immunity markers, including the glycolytic and mTOR pathway, were analyzed in whole tissue or isolated synoviocytes. A group of mice was treated with Rapamycin, an mTOR inhibitor before LPS or S. aureus stimulation.

Results

The double LPS – S. aureus hit promoted intense joint inflammation and damage compared to single joint stimulation, including markers in synoviocyte activation, production of proinflammatory cytokines, persistent nociception, and bone damage, despite not reducing the bacterial clearance. The double LPS - S. aureus hit joints increased the synovial macrophage population expressing CX3CR1 alongside triggering established epigenetic modifications associated with trained immunity events in these cells, such as the upregulation of the mTOR signaling pathway (p-mTOR and HIF1α) and the trimethylation of histone H3. Mice treated with Rapamycin presented reduced CX3CR1+ macrophage activation, joint inflammation, and bone damage.

Conclusions

There is a trained immunity phenotype in CX3CR1+ synovial macrophages that contributes to the exacerbation of joint inflammation and damage during septic arthritis caused by S. aureus.
Appendix
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Metadata
Title
Trained immunity of synovial macrophages is associated with exacerbated joint inflammation and damage after Staphylococcus aureus infection
Authors
Peter Silva Rocha
Adryan Aparecido Silva
Celso Martins Queiroz-Junior
Amanda Dias Braga
Thaiane Pinto Moreira
Mauro Martins Teixeira
Flávio Almeida Amaral
Publication date
28-09-2024
Publisher
Springer International Publishing
Published in
Inflammation Research / Issue 11/2024
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-024-01946-w

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