Effects of IL-34 vs M-CSF Maturation on Macrophage Interactions with Porphyromonas gingivalis
Almarghlani, Ammar AbdulBasit
MetadataShow full item record
Background: Periodontal disease is a complex multifactorial disease involving gram-negative anaerobic bacteria that can lead to the destruction of tooth supporting tissue. Tissue-resident macrophages are important for both homeostasis and coordinating an immune response. IL-34 is a ligand for CSF1R, and is capable of supporting the viability and differentiation of macrophages from monocytes in the absence of the canonical ligand M-CSF. IL-34 is important for the development of epidermal immunity, including in the oral environment, and is produced by gingival tissue at higher levels than M-CSF in response to inflammatory conditions. However, any role for IL-34 in modulating monocyte and macrophage function in gingival tissue during the development of periodontal disease in terms of cytokine expression and response to the pathogen Porphymonas gingivalis are unknown. Aim: Determine the differences in the cytokine response as well as the ability of IL-34- and M-CSF-matured macrophages to phagocytose and destroy the oral pathogen P. gingivalis . Materials and Methods: Human mononuclear cells were isolated from whole peripheral blood obtained from healthy donors and were differentiated into macrophages using either M-CSF or IL-34. The P. gingivalis uptake and intracellular clearance capability of macrophages was determined by an antibiotic protection-based assay. Flow cytometry analysis was performed on differentiated macrophages to quantify cell surface proteins known to interact with P. gingivalis , and ELISA assays were used to test for cytokine release differences between the macrophage types upon interaction with P. gingivalis . Results: IL-34 has the capability to differentiate human peripheral blood monocytes into macrophages as efficiently as M-CSF. However, IL-34 differentiated macrophages showed a significantly lower ability to internalize P. gingivalis , kill those bacteria that were engulfed, and expressed lower levels of inflammatory cytokines such as TNF, than macrophages matured with M-CSF. Conclusion: These results suggest the presence of IL-34 in gingival tissue can play a role in altering infiltrating monocyte development during the progression of periodontal disease leading to an altered ability to effectively deal with pathogenic microbes.