IRG and GBP Host Resistance Factors Target Aberrant, "Non-self" Vacuoles Characterized by the Missing of "Self" IRGM Proteins: e1003414

• Published in: PLoS pathogens 2013-06, Vol.9 (6)
• Main Authors: Haldar, Arun K, Saka, Hector A, Piro, Anthony S, Dunn, Joe Dan, Henry, Stanley C, Taylor, Gregory A, Frickel, Eva M, Valdivia, Raphael H, Coers, Jörn
• Format: Article
• Language: English
• Subjects: Autophagy; Chlamydia trachomatis; Defense mechanisms; Experiments; Interferon; Pathogens; Proteins; Signal transduction; Software; Toxoplasma gondii
• ISSN: 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1003414

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