IRG and GBP host resistance factors target aberrant, "non-self" vacuoles characterized by the missing of "self" IRGM proteins.
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....
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1003414&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850138278082117632 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Arun K Haldar |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d850e28d862a44b7a4c21959a7baf791 |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-d850e28d862a44b7a4c21959a7baf7912025-08-20T02:30:37ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742013-01-0196e100341410.1371/journal.ppat.1003414IRG and GBP host resistance factors target aberrant, "non-self" vacuoles characterized by the missing of "self" IRGM proteins.Arun K HaldarHector A SakaAnthony S PiroJoe Dan DunnStanley C HenryGregory A TaylorEva M FrickelRaphael H ValdiviaJörn CoersInterferon-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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1003414&type=printable |
| spellingShingle | 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 IRG and GBP host resistance factors target aberrant, "non-self" vacuoles characterized by the missing of "self" IRGM proteins. PLoS Pathogens |
| title | IRG and GBP host resistance factors target aberrant, "non-self" vacuoles characterized by the missing of "self" IRGM proteins. |
| title_full | IRG and GBP host resistance factors target aberrant, "non-self" vacuoles characterized by the missing of "self" IRGM proteins. |
| title_fullStr | IRG and GBP host resistance factors target aberrant, "non-self" vacuoles characterized by the missing of "self" IRGM proteins. |
| title_full_unstemmed | IRG and GBP host resistance factors target aberrant, "non-self" vacuoles characterized by the missing of "self" IRGM proteins. |
| title_short | IRG and GBP host resistance factors target aberrant, "non-self" vacuoles characterized by the missing of "self" IRGM proteins. |
| title_sort | irg and gbp host resistance factors target aberrant non self vacuoles characterized by the missing of self irgm proteins |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1003414&type=printable |
| work_keys_str_mv | AT arunkhaldar irgandgbphostresistancefactorstargetaberrantnonselfvacuolescharacterizedbythemissingofselfirgmproteins AT hectorasaka irgandgbphostresistancefactorstargetaberrantnonselfvacuolescharacterizedbythemissingofselfirgmproteins AT anthonyspiro irgandgbphostresistancefactorstargetaberrantnonselfvacuolescharacterizedbythemissingofselfirgmproteins AT joedandunn irgandgbphostresistancefactorstargetaberrantnonselfvacuolescharacterizedbythemissingofselfirgmproteins AT stanleychenry irgandgbphostresistancefactorstargetaberrantnonselfvacuolescharacterizedbythemissingofselfirgmproteins AT gregoryataylor irgandgbphostresistancefactorstargetaberrantnonselfvacuolescharacterizedbythemissingofselfirgmproteins AT evamfrickel irgandgbphostresistancefactorstargetaberrantnonselfvacuolescharacterizedbythemissingofselfirgmproteins AT raphaelhvaldivia irgandgbphostresistancefactorstargetaberrantnonselfvacuolescharacterizedbythemissingofselfirgmproteins AT jorncoers irgandgbphostresistancefactorstargetaberrantnonselfvacuolescharacterizedbythemissingofselfirgmproteins |