IRG and GBP Host Resistance Factors Target Aberrant, “Non-self” Vacuoles Characterized by the Missing of “Self” IRGM Proteins

• DOI: 10.1371/journal.ppat.1003414
• Publication Date: 2013-06-13T20:56:11Z
• Authors: Arun K. Haldar; Hector A. Saka; Anthony S. Piro; Joe Dan Dunn; Stanley C. Henry; Gregory A. Taylor; Eva M. Frickel; Raphael H. Valdivia; Jörn Coers
• Keywords: Intracellular parasite; Organelle

Interferon-inducible GTPases of the Immunity Related GTPase (IRG) and Guanylate Binding Protein (GBP) families provide resistance to intracellular pathogenic microbes. IRGs GBPs stably associate with pathogen-containing vacuoles (PVs) elicit immune pathways directed at targeted vacuoles. Targeting PVs requires formation higher-order protein oligomers, a process negatively regulated by subclass IRG proteins called IRGMs. We found that paralogous IRGM Irgm1 Irgm3 fail robustly "non-self" containing either bacterial pathogen Chlamydia trachomatis or protozoan Toxoplasma gondii. Instead, reside on "self" organelles including lipid droplets (LDs). Whereas IRGM-positive LDs are guarded against stable association other GBPs, we demonstrate IRGM-stripped become high affinity binding substrates for GBP proteins. These data reveal recognition organelle-like structures is partly dictated missing from these structures.