Fibroblasts modulate pulp inflammation and initiate healing: the added value of fibroblast-macrophage interactions.

Pulp tissue resides within rigid dentinal walls and depends on terminal circulation, making its healing capacity highly contingent on the degree of inflammation and suggesting the presence of intrinsic protective mechanisms to prevent necrosis. Multiple cell types including odontoblasts, fibroblasts, endothelial cells, and inflammatory cells, contribute to these mechanisms through the synthesis of bioactive molecules. Odontoblasts and pulp fibroblasts detect pathogen-associated molecular patterns via Toll-like receptors and release pro-inflammatory cytokines such as IL-6, IL-8, and TNF-α. These mediators, also produced during sterile inflammation, recruit phagocytic cells that clear pathogens and tissue debris. Pulp fibroblasts further contribute to innate defense by constitutively generating Complement components, including C3b, which opsonizes cariogenic bacteria, and the membrane attack complex, which lyses microbes. Physical injury or exposure to bacterial components enhances fibroblast production of these molecules, demonstrating potent local modulation during carious or traumatic insult. Beyond antimicrobial roles, fibroblasts influence repair by regulating stem cell recruitment and differentiation via Complement activation. They also participate in macrophage recruitment and polarization into M1 and M2 subsets. While M1 macrophages primarily mediate pathogen clearance, both phenotypes contribute to the early stages of pulp healing. This review examines key mechanisms governing local control of pulpal inflammation and repair, emphasizing emerging evidence that fibroblast-macrophage interactions and macrophage polarization are central regulators of both inflammatory resolution and initiation of tissue regeneration.