Interferon-gamma impairs phagocytosis of by primary murine peritoneal macrophages stimulated with LPS and differentially modulates proinflammatory cytokine release.

Introduction: Interferon-γ levels are increased upon viral infections and during inflamm-aging. Resistance to infections due to (), a major cause of bacteriaemia and sepsis, is impaired in aged individuals, partly due to altered phagocytic capacity and cytokine release of immune cells. Here, we analyzed the effect of IFN-γ on phagocytosis of K1 and release of proinflammatory cytokines by macrophages in resting condition and upon stimulation with different bacterial Toll-like receptor (TLR) agonists.

Methods: Primary peritoneal macrophages from C57BL/6 mice were exposed to medium or stimulated with agonists of TLR4 (LPS), 1/2 (PamCSK), and 9 (CpG-DNA) in the presence and absence of IFN-γ (100 U/ml) for 24 h. TNF-α, IL-6, and KC were measured in the cell culture supernatant by ELISA. Macrophages were exposed to viable K1. After 90 min, intracellular phagozytosed bacteria were quantified by quantitative plating.

Results: Macrophages treated with LPS 1 µg/ml in the presence of IFN-γ ingested more than 10-fold lower numbers of than macrophages treated with LPS alone. Phagocytosis of by macrophages in resting condition or upon stimulation with PamCSK or CpG was not significantly affected by IFN-γ. Cytokine release was differentially modulated by IFN-γ, with reduced KC release by TLR-stimulated macrophages in the presence of IFN-γ being the most striking effect.

Conclusions: , IFN-γ reduces the phagocytosis of by LPS-stimulated macrophages and differentially modulates cytokine release of macrophages activated by different bacterial TLR agonists. Elevated levels of IFN-γ might lead to reduced bacterial clearance and worse outcome of bacterial infections, e.g., in aged individuals and after viral infections and other inflammatory events.