Maggot Secretions Skew Monocyte-Macrophage Differentiation Away from a Pro-Inflammatory to a Pro-Angiogenic Type

Background: Maggots of the blowfly Lucilia sericata are used for the treatment of chronic wounds. Earlier we reported maggot secretions to inhibit pro-inflammatory responses of human monocytes. The aim of this study was to investigate the effect of maggot secretions on the differentiation of monocytes into pro-inflammatory (MO-1) and anti-inflammatory/proangiogenic macrophages (MO-2) as these cells play a central role in wound healing. Methodology/Principal Findings: Freshly isolated monocytes were incubated with secretions and GM-CSF or M-CSF for 6 days and then stimulated with LPS or LTA for 18 h. The expression of cell surface molecules and the levels of cytokines, chemokines and growth factors in supernatants were measured. Our results showed secretions to affect monocyte-macrophage differentiation leading to MO-1 with a partial MO-2-like morphology but lacking CD163, which is characteristic for MO-2. In response to LPS or LTA, secretions-differentiated MO-1 produced less pro-inflammatory cytokines (TNF-alpha, IL-12p40 and MIF) than control cells. Similar results were observed for MO-2 when stimulated with low concentrations of LPS. Furthermore, secretions dose-dependently led to MO-1 and MO-2 characterized by an altered chemokine production. Secretions led to MO-2, but not MO-1, producing enhanced levels of the growth factors bFGF and VEGF, as compared to control cells. The expression of cell-surface receptors involved in LPS/LTA was enhanced by secretions, that of CD86 and HLA-DR down-regulated, while receptors involved in phagocytosis remained largely unaffected. Conclusions: Maggot secretions skew the differentiation of monocytes into macrophages away from a pro-inflammatory to a pro-angiogenic type.