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.