Identification of an immune regulated phagosomal Rab cascade in macrophages

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Abstract

Interferon-γ (IFN-γ) has been shown to regulate phagosome trafficking and function in macrophages but the molecular mechanisms involved are poorly understood. Here, we identify Rab20 as part of the machinery by which IFN-γ controls phagosome maturation. IFN-γ stimulated Rab20 association with early phagosomes in macrophages. Using single phagosome imaging in live cells, we found that Rab20 induced an early delay in phagosome maturation and extended the time Rab5a and phosphatidylinositol 3-phosphate (PI3P) remains associated with phagosomes. Moreover, Rab20 depletion in macrophages abrogated the phagosome maturation delay induced by IFN-γ. Finally, we demonstrate that Rab20 interacts with the Rab5 guanine nucleotide exchange factor Rabex-5 and that Rab20 knockdown impaired the IFN-γ-dependent Rabex-5/Rab5a recruitment into phagosomes. Altogether, we uncover here Rab20 as a key player in the Rab cascade by which IFN-γ induces a delay in phagosome maturation in macrophages.