Autophagy activation by interferon-γ via the p38 mitogen-activated protein kinase signalling pathway is involved in macrophage bactericidal activity.

Macrophages are involved in many essential immune functions. Their role in cell-autonomous innate immunity is reinforced by interferon-γ (IFN-γ), which is mainly secreted by proliferating type 1 T helper cells and natural killer cells. Previously, we showed that IFN-γ activates autophagy via p38 mitogen-activated protein kinase (p38 MAPK), but the biological importance of this signalling pathway has not been clear.

Observation of autophagosome maturation in the interferon-γ-primed and lipopolysaccharide-activated macrophages using a tandem fluorescent tagged LC3.

Macrophages are engaged in many essential host functions, and their activation is a dynamic process that results in diverse functional outcomes such as the potentiation of bactericidal activity and production of chemokines, cytokines, and mediators that coordinate the inflammatory response. This pro-inflammatory response is bimodal, comprising a "prime" event, classically through interferon-γ (IFN-γ), and a "trigger," such as lipopolysaccharide (LPS). Recently, autophagy, which is one of the major degradative pathways in eukaryotic cells, has been shown to play an important role in both IFN-γ-primed and LPS-activated macrophages.