Fibroblasts control macrophage differentiation during pulp inflammation

Chloé Le Fournis, Charlotte Jeanneau, Thomas Giraud, Ikhlas El Karim, Fionnuala T. Lundy, Imad About*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


During pulp inflammation, recruited macrophages can differentiate into two phenotypes: pro-inflammatory M1 and anti-inflammatory M2. Pulp fibroblasts have previously been shown to regulate pulp inflammation via cytokine and growth factor secretion. We hypothesized that, upon carious injury, pulp fibroblasts interact with macrophages and modulate their differentiation.

Cultures of pulp fibroblasts were physically injured and incubated with lipoteichoic acid (LTA) to mimic the pulp environment underlying a carious lesion. Physical injuries without LTA were performed on cultured fibroblasts to simulate the surrounding pulp tissue. Fibroblast supernatants were collected and added to undifferentiated macrophages to study their differentiation into M1 or M2 phenotypes by investigating cytokine secretion profiles and phagocytosis capacity. Histological staining and immunofluorescence were performed on healthy and carious human tooth sections to localize the two macrophage phenotypes.

LTA-stimulated fibroblasts induced macrophage differentiation into M1 phenotype with a significant increase both in TNF-α secretion and phagocytosis capacity. By contrast, injured fibroblasts without LTA, led to M2 differentiation with a significant increase in IL-10 secretion and low phagocytosis capacity. In carious teeth, M1 macrophages were detected mainly in the pulp zone underlying caries, while M2 were detected in the peripheral inflammatory zone.

Fibroblasts induced macrophage differentiation to pro-inflammatory M1 with high bacteria phagocytosis capacity to control infection at the carious front. Fibroblasts located at the periphery of the inflammatory zone induced macrophage differentiation to anti-inflammatory M2. The fine balance between the two phenotypes may represent a pre-requisite for initiating the healing process.
Original languageEnglish
JournalJournal of Endodontics
Early online date26 Jun 2021
Publication statusEarly online date - 26 Jun 2021


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