Figure 2.

Illustration of the cellular context and key processes in which MPEG1 is implicated. (i) MPEG1 is constitutively expressed in macrophages and phagocytes. (ii, iii, iv) Type II IFN, TNFα and LPS signaling are involved in the regulation of MPEG1 expression. (v) Surface bound MPEG1 is essential for the correct assembly and signaling of the type I IFN pathway. (vi) MPEG1 is expressed either as a membrane tethered isoform (MPEG1) or as a secreted, truncated form (MPEG1b). (vii) LPS and IFNγ signaling are important for triggering monoubiquitination of MPEG1 in EEA1⁺ vesicles. Some pathogens produce CIF which inhibits the monoubiquitination of MPEG1 and confers resistance. (viii) Once monoubiquitinated, EEA1⁺/MPEG1⁺ vesicles traffic to and fuse with the early phagosome. The phagocytic and secretory pathways cooperate to enrich intracellular compartments with MPEG1 to aid in the disruption and killing of engulfed microbes. Proteases (scissors) may be important for MPEG1 function. (ix) As phagosomal and endosomal vesicles become acidified, MPEG1 is activated to form lytic pores. Figure produced with BioRender.