%0 Journal Article
%T IRG and GBP Host Resistance Factors Target Aberrant, ¡°Non-self¡± Vacuoles Characterized by the Missing of ¡°Self¡± IRGM Proteins
%A Arun K. Haldar
%A Hector A. Saka
%A Anthony S. Piro
%A Joe Dan Dunn
%A Stanley C. Henry
%A Gregory A. Taylor
%A Eva M. Frickel
%A Raphael H. Valdivia
%A J£¿rn Coers
%J PLOS Pathogens
%D 2013
%I Public Library of Science (PLoS)
%R 10.1371/journal.ppat.1003414
%X 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.
%U http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003414