Defined particle ligands trigger specific defense mechanisms of macrophages

Abstract

Phagocytosis is a receptor-mediated process for sequestration and inactivation of infectious microbes. It can be triggered by microbial surface compounds or particle-attached host proteins. We monitored the effector functions of murine bone marrow-derived macrophages (BMMs) in response to polystyrene-streptavidin beads coated with the defined ligands IgG1, β-glucan, mannan, complement factors C1q or iC3b, or fibronectin (FN). Cell-autonomous effector mechanisms (uptake, phagosome maturation, cytokine responses and killing activity) were differentially triggered. All particle-ligand complexes stimulated the release of nitric oxide, but only beads coated with IgG, complement factors or FN caused production of superoxide. Beads coated with C1q, iC3b or FN strongly stimulated the secretion of pro-inflammatory TNF-α, IL-6, and IL-1β and also of anti-inflammatory IL-10. Escherichia coli coated with C1q, iC3b or FN was killed much less efficiently than with any of the other ligands, depending on the presence of IL-10 activity. This indicated an important role of IL-10 as regulator of cell-autonomous immune functions of macrophages. Our data show that defined ligands on microbial surfaces are interesting candidates to activate innate defense mechanisms selectively and specifically. © The Author(s) 2010.