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IRG and GBP Host Resistance Factors Target Aberrant,Non-self Vacuoles Characterized by the Missing of Self IRGM Proteins
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نویسنده
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haldar a.k. ,saka h.a. ,piro a.s. ,da dunn j. ,henry s.c. ,taylor g.a. ,frickel e.m. ,valdivia r.h. ,coers j.
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منبع
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plos pathogens - 2013 - دوره : 9 - شماره : 6
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چکیده
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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.
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آدرس
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departments of molecular genetics and microbiology,and immunology,duke university medical center,durham,nc, United States, department of molecular genetics and microbiology,duke university medical center,durham,nc, United States, departments of molecular genetics and microbiology,and immunology,duke university medical center,durham,nc, United States, department of molecular genetics and microbiology,duke university medical center,durham,nc, United States, departments of medicine,molecular genetics and microbiology,and immunology,center for the study of aging,duke university,durham,nc,united states,geriatric research and education and clinical center,veteran affairs medical center,durham,nc, United States, departments of medicine,molecular genetics and microbiology,and immunology,center for the study of aging,duke university,durham,nc,united states,geriatric research and education and clinical center,veteran affairs medical center,durham,nc, United States, division of parasitology,mrc national institute for medical research,london, United Kingdom, department of molecular genetics and microbiology,duke university medical center,durham,nc, United States, departments of molecular genetics and microbiology,and immunology,duke university medical center,durham,nc, United States
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Authors
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